Science.gov

Sample records for antidepressant nonresponders studied

  1. The Auditory P3 in Antidepressant Pharmacotherapy Treatment Responders, Non-Responders and Controls

    PubMed Central

    Jaworska, Natalia; De Somma, Elisea; Blondeau, Claude; Tessier, Pierre; Norris, Sandhaya; Fusee, Wendy; Smith, Dylan; Blier, Pierre; Knott, Verner

    2013-01-01

    Event-related potentials (ERPs), derived from electroencephalographic (EEG) recordings, can index electrocortical activity related to cognitive operations. The fronto-central P3a ERP is involved in involuntary processing of novel auditory information, whereas the parietal P3b indexes controlled attention processing. The amplitude of the auditory P3b has been found to be decreased in major depressive disorder (MDD). However, few studies have examined the relationship between the P3b, the related P3a, and antidepressant treatment response. We tested 53 unmedicated individuals (25 females) with MDD as well as 43 non-depressed controls (23 females) on the novelty oddball task, wherein infrequent deviant (target) and frequent standard (non-target) tones were presented, along with infrequent novel (non-target/distractor) sounds. The P3a and P3b ERPs were assessed to the novel and target sounds, respectively, as were accompanying behavioural performance measures. Depression ratings and antidepressant response status were assessed following 12 weeks of pharmacotherapy with three different regimens. Antidepressant treatment non-responders had smaller baseline P3a/b amplitudes than responders and healthy controls. Baseline P3b amplitude also weakly predicted the extent of depression rating changes by week 12. Females exhibited larger P3a/b amplitudes than males. With respect to task performance, controls had more target hits than treatment non-responders. ERP measures correlated with clinical changes in males and with behavioural measures in females. These results suggest that greater (or control-like) baseline P3a/b amplitudes are associated with a positive antidepressant response, and that gender differences characterize the P3 and, hence, basic attentive processes. PMID:23664712

  2. A prospective trial of bupropion SR augmentation of partial and non-responders to serotonergic antidepressants.

    PubMed

    DeBattista, Charles; Solvason, H Brent; Poirier, Jennifer; Kendrick, Ellen; Schatzberg, Alan F

    2003-02-01

    Many patients fail to achieve an adequate response to a given antidepressant trial. The best-studied augmentation agents, lithium and thyroid supplementation are less commonly used. Augmenting antidepressants with bupropion has become an increasingly common strategy in the treatment of resistant depression. Several case reports and 2 open label studies suggest efficacy of this strategy. The purpose of this study is to further examine the utility of bupropion sustained release (SR) augmentation in patients with inadequate response to selective serotonin reuptake inhibitors. Patients who met DSM-IV criteria for major depression and had failed to achieve adequate response to an SSRI were considered for this study. Eligible patients were required to have a score of 16 on the 24-item Hamilton Depression Rating Scale (HDRS). Patients were treated openly for 6 weeks with bupropion SR added to their existing antidepressant. The dose range of bupropion was 150 to 300 mg per day. At each visit, patients were assessed using the Beck Depression Inventory (BDI), the Hamilton Depression Ratings Scale (HDRS), and the Clinical Global Impression (CGI). Twenty-eight patients (12 men, 16 women) entered the study. Twenty-five patients completed the six-week trial. With respect to the clinical benefit of bupropion SR augmentation, 15 out of 28, or 54% of patients, were classified as responders, showing a decrease in their HDRS or BDI scores of 50% or more between baseline and Week 6. This prospective, open-label trial supports the use of bupropion SR in the augmentation of SSRIs and venlafaxine. Placebo controlled trials should be completed to further evaluate the efficacy of this strategy.

  3. S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial.

    PubMed

    Papakostas, George I; Mischoulon, David; Shyu, Irene; Alpert, Jonathan E; Fava, Maurizio

    2010-08-01

    Despite the progressive increase in the number of antidepressants, many patients with major depressive disorder continue to be symptomatic. Clearly, there is an urgent need to develop better tolerated and more effective treatments for this disorder. The use of S-adenosyl methionine (SAMe), a naturally occurring molecule that serves as a methyl donor in human cellular metabolism, as adjunctive treatment for antidepressant nonresponders with major depressive disorder represents one such effort toward novel pharmacotherapy development. Participants were 73 serotonin reuptake inhibitor (SRI) nonresponders with major depressive disorder enrolled in a 6-week, double-blind, randomized trial of adjunctive oral SAMe (target dose: 800 mg/twice daily). Patients continued to receive their SRI treatment at a stable dose throughout the 6-week trial. The primary outcome measure for the study was the response rates according to the 17-item Hamilton Depression Rating Scale (HAM-D). The HAM-D response and remission rates were higher for patients treated with adjunctive SAMe (36.1% and 25.8%, respectively) than adjunctive placebo (17.6% versus 11.7%, respectively). The number needed to treat for response and remission was approximately one in six and one in seven, respectively. There was no statistically significant difference in the proportion of SAMe- versus placebo-treated patients who discontinued the trial for any reason (20.6% versus 29.5%, respectively), due to adverse events (5.1% versus 8.8%, respectively), or due to inefficacy (5.1% versus 11.7%, respectively). These preliminary results suggest that SAMe can be an effective, well-tolerated, and safe adjunctive treatment strategy for SRI nonresponders with major depressive disorder and warrant replication.

  4. Anti-inflammatory treatment for major depressive disorder: implications for patients with an elevated immune profile and non-responders to standard antidepressant therapy

    PubMed Central

    Kopschina Feltes, Paula; Doorduin, Janine; Klein, Hans C; Juárez-Orozco, Luis Eduardo; Dierckx, Rudi AJO; Moriguchi-Jeckel, Cristina M; de Vries, Erik FJ

    2017-01-01

    Major depressive disorder (MDD) is a prevalent and disabling psychiatric disease with rates of non-responsiveness to antidepressants ranging from 30–50%. Historically, the monoamine depletion hypothesis has dominated the view on the pathophysiology of depression. However, the lack of responsiveness to antidepressants and treatment resistance suggests that additional mechanisms might play a role. Evidence has shown that a subgroup of depressive patients may have an underlying immune deregulation that could explain the lack of therapeutic benefit from antidepressants. Stimuli like inflammation and infection can trigger the activation of microglia to release pro-inflammatory cytokines, acting on two main pathways: (1) activation of the hypothalamic–pituitary adrenal axis, generating an imbalance in the serotonergic and noradrenergic circuits; (2) increased activity of the enzyme indoleamine-2,3-dioxygenase, resulting in depletion of serotonin levels and the production of quinolinic acid. If this hypothesis is proven true, the subgroup of MDD patients with increased levels of pro-inflammatory cytokines, mainly IL-6, TNF-α and IL-1β, might benefit from an anti-inflammatory intervention. Here, we discuss the pre-clinical and clinical studies that have provided support for treatment with non-steroidal anti-inflammatory drugs in depressed patients with inflammatory comorbidities or an elevated immune profile, as well as evidences for anti-inflammatory properties of standard antidepressants. PMID:28653857

  5. Anti-inflammatory treatment for major depressive disorder: implications for patients with an elevated immune profile and non-responders to standard antidepressant therapy.

    PubMed

    Kopschina Feltes, Paula; Doorduin, Janine; Klein, Hans C; Juárez-Orozco, Luis Eduardo; Dierckx, Rudi Ajo; Moriguchi-Jeckel, Cristina M; de Vries, Erik Fj

    2017-09-01

    Major depressive disorder (MDD) is a prevalent and disabling psychiatric disease with rates of non-responsiveness to antidepressants ranging from 30-50%. Historically, the monoamine depletion hypothesis has dominated the view on the pathophysiology of depression. However, the lack of responsiveness to antidepressants and treatment resistance suggests that additional mechanisms might play a role. Evidence has shown that a subgroup of depressive patients may have an underlying immune deregulation that could explain the lack of therapeutic benefit from antidepressants. Stimuli like inflammation and infection can trigger the activation of microglia to release pro-inflammatory cytokines, acting on two main pathways: (1) activation of the hypothalamic-pituitary adrenal axis, generating an imbalance in the serotonergic and noradrenergic circuits; (2) increased activity of the enzyme indoleamine-2,3-dioxygenase, resulting in depletion of serotonin levels and the production of quinolinic acid. If this hypothesis is proven true, the subgroup of MDD patients with increased levels of pro-inflammatory cytokines, mainly IL-6, TNF-α and IL-1β, might benefit from an anti-inflammatory intervention. Here, we discuss the pre-clinical and clinical studies that have provided support for treatment with non-steroidal anti-inflammatory drugs in depressed patients with inflammatory comorbidities or an elevated immune profile, as well as evidences for anti-inflammatory properties of standard antidepressants.

  6. Antidepressant Studies in Parkinson’s Disease

    PubMed Central

    Weintraub, Daniel; Morales, Knashawn H.; Moberg, Paul J.; Bilker, Warren B.; Balderston, Catherine; Duda, John E.; Katz, Ira R.; Stern, Matthew B.

    2007-01-01

    The objective of this study was to determine effect sizes for both antidepressant treatment and placebo for depression in Parkinson’s disease (PD), and to compare the findings with those reported in elderly depressed patients without PD. Recent reviews have concluded that there is little empiric evidence to support the use of antidepressants in PD; however, available data has not been analyzed to determine the effect size for antidepressant treatment in PD depression. A literature review identified antidepressant studies in PD. Suitable studies were analyzed using meta-analytic techniques, and effect sizes were compared with those from antidepressant studies in elderly patients without PD. Large effect sizes were found for both active treatment and placebo in PD, but there was no difference between the two groups. In contrast, active treatment was superior to placebo in depressed elderly patients without PD. In PD, increasing age and a diagnosis of major depression were associated with better treatment response. Results also suggest that newer antidepressants are well tolerated in PD. Despite the high prevalence of depression and antidepressant use in PD, controlled treatment research has been almost non-existent. Meta-analysis results suggest a large but nonspecific effect for depression treatment in PD. In addition, PD patients may benefit less from antidepressant treatment, particularly selective serotonin reuptake inhibitors, than do elderly patients without PD. PMID:15954137

  7. Antidepressants

    MedlinePlus

    Antidepressants are medicines that treat depression. Your doctor can prescribe them for you. They work to balance ... them to help. There are several types of antidepressants. You and your doctor may have to try ...

  8. [Bias due to non-responders in an epidemiological study (SAPALDIA)].

    PubMed

    Luthi, J C; Zellweger, J P; Grize, L; Leuenberger, P; Ackermann-Liebrich, U

    1997-01-01

    Within the Swiss Study on Air Pollution and Lung Diseases in Adults (SAPALDIA) 16267 adults aged 18 to 60 years from 8 different locations in Switzerland were randomly selected for answering a questionnaire about respiratory health and have a lung function examination with allergy test. 9561 subjects agreed with the examination (59%) (= responders, R). In order to study the possible influence of the bias introduced by non-responders (NR), 221 subjects who refused to participate among the 966 first subjects selected in Payerne were contacted by phone. 142 accepted a home visit and answered a shortened questionnaire about the main respiratory symptoms and diseases and indicated furthermore the reasons for their refusal. Non-responders have a lower mean educational level and belong to lower social classes than responders. The frequency of respiratory symptoms and diseases, allergies and smoking is similar in R and NR except a higher frequency of wheezing during the last 12 month (R: 12.5%, NR: 5.6%, p = 0.03). The level of carbon monoxide in expired air is higher in NR (17.6 ppm) that in R (11.9 ppm) (p = 0.01). A similar difference exists between NR (30.7 pp) and R (24.8 ppm) among current smokers (p < 0.01). The main reasons for refusal are lack of time (27.5%), lack of interest for medical study (22.6%), fear of health professionals (18.3%) or the existence of a another disease (9.9%). Furthermore, 2.8% of the subjects consider a medical study as useless and refuse principally any participation. The role of local press and media in the decision to participate seems to be important. Globally, the differences between R and NR are minimal and should not influence the validity of the results of the SAPALDIA study.

  9. Pharmacogenomic study in patients with multiple sclerosis: Responders and nonresponders to IFN-β.

    PubMed

    Bustamante, Marta F; Morcillo-Suárez, Carlos; Malhotra, Sunny; Rio, Jordi; Leyva, Laura; Fernández, Oscar; Zettl, Uwe K; Killestein, Joep; Brassat, David; García-Merino, Juan Antonio; Sánchez, Antonio J; Urcelay, Elena; Alvarez-Lafuente, Roberto; Villar, Lusia M; Alvarez-Cermeño, Jose Carlos; Farré, Xavier; Lechner-Scott, Jeannette; Vandenbroeck, Koen; Rodríguez-Antigüedad, Alfredo; Drulovic, Jelena S; Martinelli Boneschi, Filippo; Chan, Andrew; Oksenberg, Jorge; Navarro, Arcadi; Montalban, Xavier; Comabella, Manuel

    2015-10-01

    We aimed to investigate the association between polymorphisms located in type I interferon (IFN)-induced genes, genes belonging to the toll-like receptor (TLR) pathway, and genes encoding neurotransmitter receptors and the response to IFN-β treatment in patients with multiple sclerosis (MS). In a first or screening phase of the study, 384 polymorphisms were genotyped in 830 patients with MS classified into IFN-β responders (n = 416) and nonresponders (n = 414) according to clinical criteria. In a second or validation phase, the most significant polymorphisms associated with IFN-β response were genotyped in an independent validation cohort of 555 patients with MS (281 IFN-β responders and 274 nonresponders). Seven single nucleotide polymorphisms (SNPs) were selected from the screening phase for further validation: rs832032 (GABRR3; p = 0.0006), rs6597 (STUB1; p = 0.019), rs3747517 (IFIH1; p = 0.010), rs2277302 (PELI3; p = 0.017), rs10958713 (IKBKB; p = 0.003), rs2834202 (IFNAR1; p = 0.030), and rs4422395 (CXCL1; p = 0.017). None of these SNPs were significantly associated with IFN-β response when genotyped in an independent cohort of patients. Combined analysis of these SNPs in all patients with MS (N = 1,385) revealed 2 polymorphisms associated with IFN-β response: rs2277302 (PELI3; p = 0.008) and rs832032 (GABRR3; p = 0.006). These findings do not support an association between polymorphisms located in genes related to the type I IFN or TLR pathways or genes encoding neurotransmitter receptors and the clinical response to IFN-β. Nevertheless, additional genetic and functional studies of PELI3 and GABRR3 are warranted.

  10. What is wrong with non-respondents? Alcohol-, drug- and smoking-related mortality and morbidity in a 12-year follow-up study of respondents and non-respondents in the Danish Health and Morbidity Survey.

    PubMed

    Christensen, Anne Illemann; Ekholm, Ola; Gray, Linsay; Glümer, Charlotte; Juel, Knud

    2015-09-01

    Response rates in health surveys have diminished over the last two decades, making it difficult to obtain reliable information on health and health-related risk factors in different population groups. This study compared cause-specific mortality and morbidity among survey respondents and different types of non-respondents to estimate alcohol-, drug- and smoking-related mortality and morbidity among non-respondents. Prospective follow-up study of respondents and non-respondents in two cross-sectional health surveys. Denmark. A total sample of 39 540 Danish citizens aged 16 years or older. Register-based information on cause-specific mortality and morbidity at the individual level was obtained for respondents (n = 28 072) and different types of non-respondents (refusals n = 8954; illness/disabled n = 731, uncontactable n = 1593). Cox proportional hazards models were used to examine differences in alcohol-, drug- and smoking-related mortality and morbidity, respectively, in a 12-year follow-up period. Overall, non-response was associated with a significantly increased hazard ratio (HR) of 1.56 [95% confidence interval (CI) = 1.36-1.78] for alcohol-related morbidity, 1.88 (95% CI = 1.38-2.57) for alcohol-related mortality, 1.55 (95% CI = 1.27-1.88) for drug-related morbidity, 3.04 (95% CI = 1.57-5.89) for drug-related mortality and 1.15 (95% CI = 1.03-1.29) for smoking-related morbidity. The hazard ratio for smoking-related mortality also tended to be higher among non-respondents compared with respondents, although no significant association was evident (HR = 1.14; 95% CI = 0.95-1.36). Uncontactable and ill/disabled non-respondents generally had a higher hazard ratio of alcohol-, drug- and smoking-related mortality and morbidity compared with refusal non-respondents. Health survey non-respondents in Denmark have an increased hazard ratio of alcohol-, drug- and smoking-related mortality and morbidity compared with

  11. Improving study design for antidepressant effectiveness assessment.

    PubMed

    Naudet, Florian; Millet, Bruno; Reymann, Jean Michel; Falissard, Bruno

    2013-09-01

    Antidepressants effectiveness in major depressive disorder (MDD) is still questioned because the extrapolation of randomized controlled trial (RCT) results to "real life" settings is problematic. The application of the RCT paradigm in a disorder of this type, where global care plays a central role, raises questions regarding the internal and external validity of this type of study. Outcome measurement, attrition rates, the ability of the double-blind design to control for expectations, placebo response, the representativeness of trial participants and publication bias are major methodological pitfalls. This review discusses these issues. It is illustrated using original data and proposes some alternatives for assessing antidepressant effectiveness via different approaches. Some are easy to implement, such as ecological measures, qualitative approaches, improvement of analytical strategy and improvement of blinding procedures. Some are sophisticated, involving temporary deception to deal with the confounding effect of expectations, and they raise ethical issues. Others resort to external validity, this being the case in observational studies. But all are necessary to explore antidepressant effectiveness.

  12. Minoxidil dose response study in female pattern hair loss patients determined to be non-responders to 5% topical minoxidil.

    PubMed

    McCoy, J; Goren, A; Kovacevic, M; Shapiro, J

    2016-01-01

    Topical minoxidil is the only US FDA approved drug for the treatment of female pattern hair loss (FPHL). 5% minoxidil foam is only effective at re-growing hair in a minority of women (approximately 40%). Thus, the majority of FPHL patients remain untreated. Previously, we demonstrated that nonresponders to 5% minoxidil have low metabolism of minoxidil in hair follicles. As such, we hypothesized that increasing the dosage of topical minoxidil to low metabolizers would increase the number of responders without increasing the incidence of adverse events. In this study, we recruited FPHL subjects that were identified as non-responders to 5% topical minoxidil utilizing the previously validated assay for minoxidil response. Subjects were treated for 12 weeks with a novel 15% topical minoxidil solution. At 12 weeks, 60% of subjects achieved a clinically significant response based on target area hair counts (>13.7% from baseline), as well as significant improvement in global photographic assessment. None of the subjects experienced significant hemodynamic changes or any other adverse events. To the best of our knowledge, this is the first study to demonstrate the potentially beneficial effect of a higher dosage of minoxidil in FPHL subjects who fail to respond to 5% minoxidil.

  13. Changes in QEEG prefrontal cordance as a predictor of response to antidepressants in patients with treatment resistant depressive disorder: a pilot study.

    PubMed

    Bares, Martin; Brunovsky, Martin; Kopecek, Miloslav; Stopkova, Pavla; Novak, Tomas; Kozeny, Jiri; Höschl, Cyril

    2007-01-01

    Previous studies of patients with unipolar depression have shown that early decreases of EEG cordance (a new quantitative EEG method) can predict clinical response. We examined whether early QEEG decrease represents a phenomenon associated with response to treatment with different antidepressants in patients with treatment resistant depression. The subjects were 17 inpatients with treatment resistant depression. EEG data and response to treatment were monitored at baseline and after 1 and 4 weeks on an antidepressant treatment. QEEG cordance was computed at three frontal electrodes in theta frequency band. The prefrontal cordance combines complementary information from absolute and relative power of EEG spectra. Recent studies have shown that cordance correlates with cortical perfusion. Depressive symptoms were assessed using Montgomery-Asberg Depression Rating Scale (MADRS). All 17 patients completed the 4-week study. All five responders showed decreases in prefrontal cordance after the first week of treatment. Only 2 of the 12 nonresponders showed early prefrontal cordance decrease. The decrease of prefrontal QEEG cordance after week 1 in responders as well as the increase in nonresponders were both statistically significant (p-value 0.03 and 0.01, respectively) and the changes of prefrontal cordance values were different between both groups (p-value 0.001). Our results suggest that decrease in prefrontal cordance may indicate early changes of prefrontal activity in responders to antidepressants. QEEG cordance may become a useful tool in the prediction of response to antidepressants.

  14. The change of QEEG prefrontal cordance as a response predictor to antidepressive intervention in bipolar depression. A pilot study.

    PubMed

    Bares, Martin; Novak, Tomas; Brunovsky, Martin; Kopecek, Miloslav; Stopkova, Pavla; Krajca, Vladimir; Höschl, Cyril

    2012-02-01

    The aim of the study was to examine whether the change of quantitative EEG (QEEG) theta prefrontal cordance after one week of various antidepressive interventions predicts response to a 4-week treatment in patients with bipolar depression. We investigated 20 inpatients who completed a 4-week treatment. EEG data were monitored at baseline and after 1 week of treatment. QEEG cordance was computed at 3 frontal electrodes (Fp1, Fp2, Fz) in theta frequency band. Depressive symptoms and clinical status were assessed using Montgomery-Åsberg Depression Rating Scale (MADRS), Clinical Global Impression (CGI) and Young Mania Rating Scale (YMRS). Seven of 8 responders (reduction of MADRS ≥50%) and only 2 of 12 non-responders had decreased prefrontal theta cordance value after the first week of treatment (p = 0.02). The positive and negative predictive values of cordance reduction for response were 0.78 and 0.91, respectively. We also found significant differences in cordance value reductions between responders and non-responders after week 1 and higher baseline cordance in responders. The change in prefrontal theta cordance was associated with subsequent change in depressive symptoms and potentially might be a useful tool in the early detection of acute response to antidepressive interventions in bipolar depressed patients. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Genome-wide association studies in pharmacogenomics of antidepressants.

    PubMed

    Lin, Eugene; Lane, Hsien-Yuan

    2015-01-01

    Major depressive disorder (MDD) is one of the most common psychiatric disorders worldwide. Doctors must prescribe antidepressants based on educated guesses due to the fact that it is unmanageable to predict the effectiveness of any particular antidepressant in an individual patient. With the recent advent of scientific research, the genome-wide association study (GWAS) is extensively employed to analyze hundreds of thousands of single nucleotide polymorphisms by high-throughput genotyping technologies. In addition to the candidate-gene approach, the GWAS approach has recently been utilized to investigate the determinants of antidepressant response to therapy. In this study, we reviewed GWAS studies, their limitations and future directions with respect to the pharmacogenomics of antidepressants in MDD.

  16. Comparing augmentation with non-antidepressants over sticking to antidepressants after treatment failure in depression: a naturalistic study.

    PubMed

    Köhler, S; Unger, T; Hoffmann, S; Steinacher, B; Fydrich, T; Bschor, T

    2013-03-01

    Non-response to an antidepressant monotherapy in unipolar depression is quite common. Therefore strategies for subsequent treatment steps are necessary. However, there is a lack of direct comparisons of these different strategies. In this naturalistic study we compared the outcome to different strategies after failure of the primary antidepressant treatment. Failure of primary antidepressant monotherapy occurred in 135 patients. 98 of these patients have been administered 4 treatment strategies of the physicians' choice: lithium augmentation (Li-Augm), switching to another antidepressant (AD-Switch), combination of 2 antidepressants (AD-Comb) or augmentation with second generation antipsychotic (SGA-Augm). Primary outcome measure was the 17-item Hamilton rating scale for depression (HRSD). Patients who received Li-Augm or augmentation with SGAs showed significantly greater improvement in HRSD and BDI compared to patients with antidepressant switch or antidepressant combination. Remission rates for Li-Augm and SGA-Augm were 89.3% and 86.2% compared to 40.7% for AD-Switch and 42.9% for AD-Comb. Changing to another pharmacological class (Li-Augm or augmentation with SGAs) showed better treatment results than sticking to the class of antidepressants (AD-Switch and AD-Comb) after primary failure in response to antidepressant monotherapy in unipolar depression. The lack of randomization and absence of a non-response definition are design flaws. Controlled studies are required to confirm the findings of this trial. © Georg Thieme Verlag KG Stuttgart · New York.

  17. Augmentative quetiapine in partial/nonresponders with generalized anxiety disorder: a randomized, placebo-controlled study.

    PubMed

    Altamura, Alfredo Carlo; Serati, Marta; Buoli, Massimiliano; Dell'Osso, Bernardo

    2011-07-01

    Generalized anxiety disorder (GAD) is a chronic and disabling condition. The aim of this study was to evaluate the effectiveness of low-dose augmentative quetiapine (mean dose=50 mg/day) in patients with GAD and partial/no response to selective serotonin reuptake inhibitors (SSRIs). Twenty patients with GAD and partial/no response to SSRIs were randomized to quetiapine (n=10) or placebo (n=10) for 8 weeks, continuing their treatment with SSRIs. Analyses of variance with repeated measures on Hamilton Anxiety Rating Scale (HAM-A) and Clinical Global Impression (CGIs; severity of illness) were carried out at baseline and after 8 weeks and the number of responders/remitters was computed and compared between the groups. HAM-A scores at baseline were 15.60 (± 4.48) in the placebo group and 18.50 (± 6.59) in the quetiapine group, and at the end-point, HAM-A scores in the placebo group were 10.40 (± 4.88) and 9.20 (± 5.86) in the quetiapine group. A significant time-by-treatment effect was found on the HAM-A (F=5.19, P=0.035) and CGIs scores (F=19.60, P<0.001) in favor of the quetiapine group. The number of responders was numerically superior in the quetiapine group (60 vs. 30%) without reaching statistical significance (χ=1.82, degree of freedom=1, P=0.37, φ=0.30). Remitters were 40% for the quetiapine group versus 20% for the placebo group (χ=0.95, degree of freedom=1, P=0.63, φ=0.22). Low-dose augmentative quetiapine may be an useful treatment option for patients with GAD and partial/no response to SSRIs. The lack of double-blind conditions and the limited sample size may limit the confidence in the reported results. Larger randomized controlled trials are warranted to confirm these data.

  18. Sildenafil failures may be due to inadequate patient instructions and follow-up: a study on 100 non-responders.

    PubMed

    Hatzichristou, Dimitrios; Moysidis, Kyriakos; Apostolidis, Apostolos; Bekos, Athanasios; Tzortzis, Vasilios; Hatzimouratidis, Konstantinos; Ioannidis, Evangelos

    2005-04-01

    The objective of this study was to identify factors that affect efficacy response rate to sildenafil in the clinical practice. The study comprised 100 consecutive sildenafil non-responders. Mean patient age was 59+/-14.4 years and mean duration of ED 5.5+/-6.4 years. All patients underwent detailed medical and sexual history and completed the IIEF and a questionnaire regarding the previous use of sildenafil. When inadequate instructions were reported, information on the appropriate use of sildenafil was given and patients were asked to use at least 4 tablets at home. Pharmacologic efficacy was re-evaluated in a scheduled follow-up visit. Mean Erectile Function Domain (ED) of the IIEF score was 14+/-9.9. In 56 patients inappropriate use of sildenafil was recognized; 45 had never used the highest recommended dose (100 mg), 32 had taken the pill with a full stomach right after a meal, 22 had taken the pill just before the initiation of sexual activity and 12 were not aware that sexual stimulation was mandatory to achieve an erection. Furthermore, 8 patients had tried the 100mg dose, despite the presence of factors associated with sildenafil clearance reduction (renal insufficiency, cimetidine treatment). Only 34 patients reported that their physician had scheduled a follow-up visit. Following adequate dose titration and time adjustment, 31 patients responded to sildenafil; 10 patients used the 50 mg dose and 21 the 100 mg. Second and third-line treatment options were offered to the rest of the patients. ED patients may receive inadequate instructions with their prescriptions. Response rate to sildenafil may be maximized after receiving appropriate dose titration and instructions on administration. ED should be treated in the same way as other chronic conditions; follow-up is necessary to evaluate the appropriate application and pharmacologic efficacy of the proposed treatment.

  19. Treatment decisions on antidepressants in nursing homes: a qualitative study.

    PubMed

    Iden, Kristina Riis; Hjørleifsson, Stefan; Ruths, Sabine

    2011-12-01

    To explore decision-making on treatment with antidepressants among doctors and nurses in nursing homes. A qualitative study based on interviews with three focus groups comprising eight physicians engaged full time, eight physicians engaged part time, and eight registered nurses, respectively. The interview guide comprised questions on initiating, evaluating, and withdrawing treatment with antidepressants. The interviews were audio-recorded, transcribed, and analysed by systematic text condensation. The first theme was the diagnostic process. The informants expressed difficulty in differentiating between depression and sorrow resulting from loss in old age. Further, the doctors reported that they relied on nurses' observations and rarely carried out systematic diagnostic work and follow-up of patients with depression. The second theme was treatment. Antidepressants were usually the only type of treatment provided, and patients were kept on medication even though staff felt uncertain whether this was effective. The third theme was who really determines the treatment. Registered nurses reported that unskilled and auxiliary nursing staff requested drug treatment, and doctors felt some pressure from the nurses to prescribe antidepressants. This study suggests that the quality of diagnosis and treatment for depression in nursing homes needs to be improved in Norway. Doctors should be more available and take responsibility and leadership in medical decisions.

  20. Blonanserin - A Novel Antianxiety and Antidepressant Drug? An Experimental Study.

    PubMed

    Limaye, Ramchandra Prabhakar; Patil, Aditi Nitin

    2016-09-01

    Many psychiatric disorders show signs and symptoms of anxiety and depression. A drug with both, effects and lesser adverse effects is always desired. Blonanserin is a novel drug with postulated effect on anxiety and depression. The study was aimed to evaluate the effect of Blonanserin on anxiety and depression in animal models. By using elevated plus maze test and forced swimming test, the antianxiety and antidepressant effects were evaluated. Animal ethics protocols were followed strictly. Total 50 rats (10 rats per group) were used for each test. As a control drug diazepam and imipramine were used in elevated plus maze and forced swimming test respectively. Blonanserin was tested for 3 doses 0.075, 0.2 and 0.8mg. These doses were selected from previous references as well as by extrapolating human doses. This study showed an antianxiety effect of Blonanserin comparable to diazepam, which was statistically significant. Optimal effect was observed with 0.075mg, followed by 0.2 and 0.8mg. It also showed an antidepressant effect which was statistically significant. Optimal effect was observed at 0.2mg dose. The results showed that at a dose range of 0.075 and 0.2mg Blonanserin has potential to exert an adjuvant antianxiety and antidepressant activity in animal models. In order to extrapolate this in patient, longer clinical studies with comparable doses should be planned. The present study underlines potential of Blonanserin as a novel drug for such studies.

  1. Psychosocial work environment and antidepressant medication: a prospective cohort study

    PubMed Central

    Bonde, Jens Peter E; Munch-Hansen, Torsten; Wieclaw, Joanna; Westergaard-Nielsen, Niels; Agerbo, Esben

    2009-01-01

    Background Adverse psychosocial work environments may lead to impaired mental health, but it is still a matter of conjecture if demonstrated associations are causal or biased. We aimed at verifying whether poor psychosocial working climate is related to increase of redeemed subscription of antidepressant medication. Methods Information on all antidepressant drugs (AD) purchased at pharmacies from 1995 through 2006 was obtained for a cohort of 21,129 Danish public service workers that participated in work climate surveys carried out during the period 2002–2005. Individual self-reports of psychosocial factors at work including satisfaction with the work climate and dimensions of the job strain model were obtained by self-administered questionnaires (response rate 77,2%). Each employee was assigned the average score value for all employees at his/her managerial work unit [1094 units with an average of 18 employees (range 3–120)]. The risk of first-time AD prescription during follow-up was examined according to level of satisfaction and psychosocial strain by Cox regression with adjustment for gender, age, marital status, occupational status and calendar year of the survey. Results The proportion of employees that received at least one prescription of ADs from 1995 through 2006 was 11.9% and prescriptions rose steadily from 1.50% in 1996 to the highest level 6.47% in 2006. ADs were prescribed more frequent among women, middle aged, employees with low occupational status and those living alone. None of the measured psychosocial work environment factors were consistently related to prescription of antidepressant drugs during the follow-up period. Conclusion The study does not indicate that a poor psychosocial work environment among public service employees is related to prescription of antidepressant pharmaceuticals. These findings need cautious interpretation because of lacking individual exposure assessments. PMID:19635130

  2. How does media coverage effect the consumption of antidepressants? A study of the media coverage of antidepressants in Danish online newspapers 2010-2011.

    PubMed

    Green Lauridsen, Michael; Kälvemark Sporrong, Sofia

    2017-08-02

    The news media has become a major source of health information for the public, and hence vital in the individuals' opinions and decisions about health topics. The first decrease in the usage of antidepressants in Denmark in over a decade happened alongside an intensive period of media coverage about antidepressants. The aim of this study was to examine the Danish media's coverage of antidepressants during 2010-2011 in order to explore what influence it could have had on the change in the use of antidepressants. Three media theoretical concepts, agenda-setting, priming and framing, were used to explain the media influence with regard to which subject the public should think about, which criteria the public should judge the subject by, and how the public should think about the subject. All articles about antidepressants in the main Danish Internet newspapers from 2010-2011 were analyzed via quantitative and qualitative content analyses. The quantitative analysis was used to determine agenda-setting (number of articles) and, by coding articles, how priming was used in the descriptions of antidepressants. In the qualitative analysis, all articles were analyzed and condensed to determine which frames were used. Quantitative results: 271 articles were included. Agenda-setting was shown by a marked increase in the number of articles about antidepressants. Eight main codes were identified, with the negatively-associated side effects being the major one, thereby priming the public to use side effects as a criterion when judging antidepressants. Qualitative results: Two main frames were identified: 1) economic profits vs. medicine safety, and 2) the necessity of antidepressants. Both frames presented a critical view on antidepressants. It is believed that the media's agenda-setting, priming and framing of antidepressants led the public to have a more skeptical view on antidepressants, which may have probably contributed to a decrease in the usage of antidepressants

  3. Treatment strategy in depression. II. MAO inhibitors in depression resistant to cyclic antidepressants: two controlled crossover studies with tranylcypromine versus L-5-hydroxytryptophan and nomifensine.

    PubMed

    Nolen, W A; van de Putte, J J; Dijken, W A; Kamp, J S; Blansjaar, B A; Kramer, H J; Haffmans, J

    1988-12-01

    Antidepressants are ineffective in about 30% of the patients with major depression. Besides electroconvulsive therapy (ECT) and lithium, MAO inhibitors have been suggested as an alternative in such patients. In 2 controlled, partial crossover studies involving 47 patients with major depression who had already been treated unsuccessfully with at least 2 cyclic antidepressants, the effect of the MAO inhibitor tranylcypromine was studied. The first study was an open comparison with L-5-hydroxytryptophan (L-5HTP), the second study a double-blind comparison with nomifensine. Neither the patients treated with L-5HTP nor the patients treated with nomifensine, except one, improved. In contrast, tranylcypromine was effective in 50% of the patients. The depressions of the responders to tranylcypromine appeared to be more endogenous (according Newcastle Scale II) and of shorter duration than those of the non-responders. It is concluded that MAO inhibitors such as tranylcypromine are an effective alternative to ECT and lithium in patients with major depression who have failed to respond to cyclic antidepressants.

  4. Venlafaxine extended release versus conventional antidepressants in the remission of depressive disorders after previous antidepressant failure: ARGOS study.

    PubMed

    Baldomero, E Baca; Ubago, J Giner; Cercós, C Leal; Ruiloba, J Vallejo; Calvo, C García; López, R Prieto

    2005-01-01

    Serotonin-norepinephrine reuptake inhibitors (SNRIs) may be used as an alternative treatment for depressed patients who do not tolerate or respond adequately to treatment with a conventional antidepressant. This randomized, open-label, multicenter study compared the effectiveness of the SNRI venlafaxine extended release (VXR) with that of conventional antidepressants (CA) in patients who were referred to an outpatient psychiatric specialty care setting for treatment after failure to tolerate or respond to at least 4 weeks of treatment with a CA in a primary care setting. Patients with a Hamilton Depression Rating Scale (HAM-D17) score > or =17 were randomly assigned to treatment with an alternative CA or VXR. Remission was defined as a score < or =7 on the HAM-D17. Efficacy analyses were carried out on 3,097 patients from the intent-to-treat (ITT) population (1,632 VXR; 1,465 CA). The antidepressants prescribed most frequently in the CA group were paroxetine (21.3%), citalopram (20.1%), sertraline (19.1%), fluoxetine (17.0%), and mirtazapine (7.9%). After 24 weeks of treatment, the VXR group demonstrated a significantly higher remission rate than did the CA group (59.3% VXR; 51.5% CA; P<.0001; odds ratio: 1.37; 95% CI: 1.19-1.58; P<.01). Despite the limitations of the open design, the results of this study suggest that venlafaxine extended release may be more effective than the conventional antidepressants used in this study when treating depressed patients who do not tolerate or respond adequately to treatment with a conventional antidepressant.

  5. Brain grey matter volume alterations associated with antidepressant response in major depressive disorder.

    PubMed

    Liu, Jia; Xu, Xin; Luo, Qiang; Luo, Ya; Chen, Ying; Lui, Su; Wu, Min; Zhu, Hongyan; Kemp, Graham J; Gong, Qiyong

    2017-09-05

    Not all patients with major depressive disorder respond to adequate pharmacological therapy. Psychoradiological studies have reported that antidepressant responders and nonresponders show different alterations in brain grey matter, but the findings are inconsistent. The present study reports a meta-analysis of voxel-based morphometric studies of patients with major depressive disorder, both antidepressant responders and nonresponders, using the anisotropic effect size version of Seed-based D Mapping to identify brain regions correlated to clinical response. A systematic search was conducted up to June 2016 to identify studies focussing on antidepressant response. In responders across 9 datasets grey matter volume (GMV) was significantly higher in the left inferior frontal gyrus and insula, while GMV was significantly lower in the bilateral anterior cingulate cortex (ACC) and the right superior frontal gyrus (SFG). In nonresponders across 5 datasets GMV was significantly lower in the bilateral ACC, median cingulate cortex (MCC) and right SFG. Conjunction analysis confirmed significant differences in the bilateral ACC and right SFG, where GMV was significantly lower in nonresponders but higher in responders. The current study adds to psychoradiology, an evolving subspecialty of radiology mainly for psychiatry and clinical psychology.

  6. /sup 13/C NMR studies of the molecular flexibility of antidepressants

    SciTech Connect

    Munro, S.L.; Andrews, P.R.; Craik, D.J.; Gale, D.J.

    1986-02-01

    The solution dynamics of a series of clinically potent antidepressants have been investigated by measuring /sup 13/C NMR relaxation parameters. Correlation times and internal motional rates were calculated from spin-lattice relaxation times and nuclear Overhauser effects for the protonated carbons in mianserin, imipramine-like antidepressants, and amitriptyline-like antidepressants. These data were interpreted in terms of overall molecular tumbling, internal rotations, and inherent flexibility of these structures. Of particular interest was the conformational variability of the tricyclic nucleus of the tricyclic antidepressants, where the data indicated a fivefold difference in mobility of the dimethylene bridge of imipramine-like antidepressants relative to amitriptyline-like compounds. The implications of such a difference in internal motions is discussed in relation to previous NMR studies and to the reported differences in pharmacological activity of these antidepressants.

  7. When is Pharmacogenetic Testing for Antidepressant Response Ready for the Clinic? A Cost-effectiveness Analysis Based on Data from the STAR*D Study

    PubMed Central

    Perlis, Roy H.; Patrick, Amanda; Smoller, Jordan W.; Wang, Philip S.

    2009-01-01

    The potential of personalized medicine to transform the treatment of mood disorders has been widely touted in psychiatry, but has not been quantified. We estimated the costs and benefits of a putative pharmacogenetic test for antidepressant response in the treatment of major depressive disorder (MDD) from the societal perspective. Specifically, we performed cost-effectiveness analyses using state-transition probability models incorporating probabilities from the multicenter STAR*D effectiveness study of MDD. Costs and quality-adjusted life years were compared for sequential antidepressant trials, with or without guidance from a pharmacogenetic test for differential response to selective serotonin reuptake inhibitors (SSRIs). Likely SSRI responders received an SSRI, while likely nonresponders received the norepinephrine/dopamine reuptake inhibitor bupropion. For a 40-year-old with major depressive disorder, applying the pharmacogenetic test and using the non-SSRI bupropion for those at higher risk for nonresponse cost $93,520 per additional quality-adjusted life-year (QALY) compared with treating all patients with an SSRI first and switching sequentially in the case of nonremission. Cost/QALY dropped below $50,000 for tests with remission rate ratios as low as 1.5, corresponding to odds ratios ~1.8–2.0. Tests for differential antidepressant response could thus become cost-effective under certain circumstances. These circumstances, particularly availability of alternative treatment strategies and test effect sizes, can be estimated and should be considered before these tests are broadly applied in clinical settings. PMID:19494805

  8. Antidepressant Prescription Pattern in the Presence of Medical Co-morbidity: REAP-AD 2013 Study.

    PubMed

    Grover, S; Avasthi, A; Tripathi, A; Tanra, A J; Chee, K Y; He, Y L; Chiu, H Fk; Kuga, H; Lee, M S; Chong, M Y; Udormatn, P; Kanba, S; Yang, S Y; Si, T M; Sim, K; Tan, C H; Shen, W W; Xiang, Y T; Sartorius, N; Shinfuku, N

    2015-09-01

    To evaluate the prescription pattern of antidepressants in patients with medical co-morbidity from major psychiatric centres in Asia. The Research on Asian Psychotropic Prescription Pattern for Antidepressants (REAP-AD 2013) collected data from 42 psychiatric centres in 10 Asian countries and regions. Antidepressant prescriptions of 2320 patients with various psychiatric disorders were evaluated. Of these, 370 patients who had specified medical co-morbidities formed the study cohort. Escitalopram (20%) and mirtazapine (20%) were the most commonly prescribed antidepressants in patients with medical co-morbidity followed by sertraline (16%), trazodone (15%), and paroxetine (12%). Overall, more than half (52%; 247/476) of prescriptions comprised selective serotonin reuptake inhibitors. Slightly less than two-thirds (63%; n = 233) of patients received at least 1 selective serotonin reuptake inhibitor. In addition, 79% of patients were prescribed only 1 antidepressant. The mean number of antidepressants used per patient was 1.25 (standard deviation, 0.56). There were subtle differences in the most preferred antidepressant across medical illnesses such as diabetes mellitus, liver dysfunction, acid peptic disease, and cerebrovascular disease. Differences were also seen in prescription patterns across different countries. Although selective serotonin reuptake inhibitors formed the bulk of antidepressant prescriptions in the presence of medical co-morbidity, mirtazapine was also commonly used in the presence of medical co-morbidities. Specified medical morbidities do influence the selection of antidepressants.

  9. Antidepressants and Valvular Heart Disease: A Nested Case-Control Study in Taiwan.

    PubMed

    Lin, Chia-Hui; Hsiao, Fei-Yuan; Liu, Yen-Bin; Gau, Susan Shur-Fen; Wang, Chi-Chuan; Shen, Li-Jiuan

    2016-04-01

    Empirical evidence regarding the association between antidepressants and valvular heart disease (VHD) is scarce.Using Taiwan's National Health Insurance Research database, this nested case-control study assessed the association between antidepressants and VHD in a Chinese population.Among a cohort of patients who used at least 3 prescription antidepressants, 874 cases with VHD and 3496 matched controls (1:4 ratio) were identified. Conditional logistic regression models were used to examine the timing, duration, dose and type of antidepressants use, and the risk of VHD.Current use of antidepressants was associated with a 1.4-fold increase in the risk of VHD (adjusted odds ratio [aOR] 1.44; 95% confidence interval [CI] 1.17-1.77). Among current users, a dose-response association was observed in terms of the cumulative duration and the cumulative antidepressant dose. Significantly higher risks of VHD were observed among the current users of tricyclic antidepressants (aOR 1.40 [1.05-1.87]).We found that the use of antidepressants was associated with a greater risk of VHD and that the risks varied according to different antidepressants.

  10. Antidepressant monotherapy and combination of antidepressants in the treatment of resistant depression in current clinical practice: A retrospective study.

    PubMed

    Bares, Martin; Novak, Tomas; Kopecek, Miloslav; Stopkova, Pavla; Höschl, Cyril

    2010-11-01

    Abstract Objectives. The aim of this study was to compare efficacy of antidepressant monotherapies and combinations of antidepressants in the treatment of resistant patients in current clinical practice. Methods. We reviewed chart documents of resistant depressive inpatients treated at least 4 weeks with a new treatment. Depressive symptoms and clinical status were assessed using Montgomery and Åsberg Depression Rating Scale (MADRS), Beck Depression Inventory-Short Form and Clinical Global Impression at the baseline, week 2 and in the end of treatment. Results. We identified 81 patients (27 with combinations and 51 with monotherapies) that were suitable for analyses. The combination group achieved higher reduction of MADRS score (14.6 vs 10.2 pts., p=0.02) and response rate (≥ 50% reduction of MADRS, 67% vs 39%, p=0.03). Number needed to treat for response was 4. Conclusions. Based on our results, we suggest that combination of antidepressants might be more effective than monotherapy in clinical practice.

  11. Child development following exposure to tricyclic antidepressants or fluoxetine throughout fetal life: a prospective, controlled study.

    PubMed

    Nulman, Irena; Rovet, Joanne; Stewart, Donna E; Wolpin, Jacob; Pace-Asciak, Pia; Shuhaiber, Samar; Koren, Gideon

    2002-11-01

    Previous work suggested that first-trimester exposure to tricyclic antidepressants or fluoxetine does not affect adversely child IQ and language development. However, many women need antidepressants throughout pregnancy to avoid morbidity and suicide attempts. Little is known about the fetal safety of tricyclic antidepressants and fluoxetine when taken throughout pregnancy. The goal of this study was to assess the effects of tricyclic antidepressants and fluoxetine used throughout gestation on child IQ, language, and behavior. In a prospective study, mother-child pairs exposed throughout gestation to tricyclic antidepressants (N=46) or fluoxetine (N=40) and an unexposed, not depressed comparison group (N=36) were blindly assessed. The three groups were compared in terms of the children's IQ, language, behavior, and temperament between ages 15 and 71 months. The authors adjusted for independent variables such as duration and severity of maternal depression, duration of pharmacological treatment, number of depression episodes after delivery, maternal IQ, socioeconomic status, cigarette smoking, and alcohol use. Neither tricyclic antidepressants nor fluoxetine adversely affected the child's global IQ, language development, or behavior. IQ was significantly and negatively associated with duration of depression, whereas language was negatively associated with number of depression episodes after delivery. Exposure to tricyclic antidepressants or fluoxetine throughout gestation does not appear to adversely affect cognition, language development, or the temperament of preschool and early-school children. In contrast, mothers' depression is associated with less cognitive and language achievement by their children. When needed, adequate antidepressant therapy should be instituted and maintained during pregnancy and postpartum.

  12. Using antidepressants and the risk of stroke recurrence: report from a national representative cohort study.

    PubMed

    Juang, Hsiao-Ting; Chen, Pei-Chun; Chien, Kuo-Liong

    2015-06-05

    Evidence about the association between antidepressants and the risk of stroke recurrence was scanty. This study evaluated the risk of stroke recurrence according to using antidepressants in patients with stroke from a national representative cohort. This cohort study followed 16770 patients aged > =20 years who had an incident stroke from 2000 to 2009 from the National Health Insurance Research Database in Taiwan. Records of each antidepressant prescription were obtained during follow-up. The types of antidepressants were categorized by Anatomical Therapeutic Chemical classification system: tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), and other antidepressants. The main outcome was a recurrent stroke during the follow-up period. The time-dependent Cox proportional hazards model was used in the analyses. During 63715 person-years of follow-up, we documented 3769 events for stroke recurrence. Antidepressants use was associated with an increased risk of stroke recurrence (adjusted hazard ratio [HR], 1.42; 95 % confidence interval [C.I.], 1.24-1.62), especially for ischemic stroke (HR, 1.48; 95 % C.I., 1.28-1.70), but not for hemorrhagic stroke (HR, 1.22; 95 % C.I., 0.86-1.73). The increased risk of stoke recurrence was found for TCAs use only (HR, 1.41; 95 % C.I., 1.14-1.74), SSRIs use only (HR, 1.31; 95 % C.I.,1.00-1.73),use of other types of antidepressants only(HR, 1.46; 95 % C.I.,1.15-1.84), or use of multiple types of antidepressants (HR, 1.84; 95 % C.I.,1.04-3.25). We demonstrated that use of antidepressants was associated with an increased risk of stroke recurrence, especially in ischemic stroke among Taiwanese. Further studies are warranted to confirm the possible underlying mechanisms of these findings.

  13. Short-term intravenous citalopram augmentation in partial/nonresponders with major depression: a randomized placebo-controlled study.

    PubMed

    Altamura, Alfredo Carlo; Dell'Osso, Bernardo; Buoli, Massimiliano; Bosi, Monica; Mundo, Emanuela

    2008-07-01

    Approximately 30-45% of patients with major depressive episode (MDE) do not fully respond to standard recommended treatments and further strategies of intervention, including pharmacological augmentation, have been proposed for these patients. This study was aimed to evaluate the efficacy of short-term, low-dose (10 mg/day) intravenous (i.v.) citalopram augmentation versus placebo in a sample of patients with MDE and partial or no response to selective serotonin reuptake inhibitors (SSRIs). Thirty-six patients with a Diagnostic and Statistical Manual for Mental Disorders, 4th edition, text revision criteria MDE and partial or no response to oral SSRIs were selected and randomly assigned to citalopram (n=18) or to placebo (n=18) i.v. augmentation. The augmentation regimen lasted 5 consecutive days during which the patients were maintained on their current treatment with oral SSRIs. Analyses of variance with repeated measures on Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale total scores, administered daily with blind-raters conditions, were done. With regard to the Hamilton Depression Rating Scale total scores, a significant time effect (F=42.02, P<0.0001) and timextreatment effect (F=21.17, P<0.0001) were found in favor of citalopram. Similar results were obtained from the analysis on Montgomery-Asberg Depression Rating Scale total scores: time effect (F=50.07, P<0.0001), timextreatment effect (F=19.91, P<0.0001), and treatment effect (F=4.07, P=0.05). Even though referred to a small sample, the present findings seem to suggest that short-term, low-dose, i.v. citalopram augmentation may be effective in depressed patients with partial or no response to oral SSRIs. Further controlled studies performed with double-blind conditions are warranted to confirm the present results.

  14. Long-term prescribing of antidepressants in the older population: a qualitative study

    PubMed Central

    Dickinson, Rebecca; Knapp, Peter; House, Allan O; Dimri, Vandana; Zermansky, Arnold; Petty, Duncan; Holmes, John; Raynor, David K

    2010-01-01

    Background High rates of long-term antidepressant prescribing have been identified in the older population. Aims To explore the attitudes of older patients and their GPs to taking long-term antidepressant therapy, and their accounts of the influences on long-term antidepressant use. Design of study Qualitative study using in-depth semi-structured interviews. Setting One primary care trust in North Bradford. Method Thirty-six patients aged ≥75 years and 10 GPs were interviewed. Patients were sampled to ensure diversity in age, sex, antidepressant type, and home circumstances. Results Participants perceived significant benefits and expressed little apprehension about taking long-term antidepressants, despite being aware of the psychological and social factors involved in onset and persistence of depression. Barriers to discontinuation were identified following four themes: pessimism about the course and curability of depression; negative expectations and experiences of ageing; medicine discontinuation perceived by patients as a threat to stability; and passive (therapeutic momentum) and active (therapeutic maintenance) decisions to accept the continuing need for medication. Conclusion There is concern at a public health level about high rates of long-term antidepressant prescribing, but no evidence was found of a drive for change either from the patients or the doctors interviewed. Any apprehension was more than balanced by attitudes and behaviours supporting continuation. These findings will need to be incorporated into the planning of interventions aimed at reducing long-term antidepressant prescribing in older people. PMID:20353660

  15. Cancer Mortality in People Treated with Antidepressants before Cancer Diagnosis: A Population Based Cohort Study.

    PubMed

    Sun, Yuelian; Vedsted, Peter; Fenger-Grøn, Morten; Wu, Chun Sen; Bech, Bodil Hammer; Olsen, Jørn; Benros, Michael Eriksen; Vestergaard, Mogens

    2015-01-01

    Depression is common after a cancer diagnosis and is associated with an increased mortality, but it is unclear whether depression occurring before the cancer diagnosis affects cancer mortality. We aimed to study cancer mortality of people treated with antidepressants before cancer diagnosis. We conducted a population based cohort study of all adults diagnosed with cancer between January 2003 and December 2010 in Denmark (N = 201,662). We obtained information on cancer from the Danish Cancer Registry, on the day of death from the Danish Civil Registry, and on redeemed antidepressants from the Danish National Prescription Registry. Current users of antidepressants were defined as those who redeemed the latest prescription of antidepressant 0-4 months before cancer diagnosis (irrespective of earlier prescriptions), and former users as those who redeemed the latest prescription five or more months before cancer diagnosis. We estimated an all-cause one-year mortality rate ratio (MRR) and a conditional five-year MRR for patients who survived the first year after cancer diagnosis and confidence interval (CI) using a Cox proportional hazards regression model. Overall, 33,111 (16.4%) patients redeemed at least one antidepressant prescription in the three years before cancer diagnosis of whom 21,851 (10.8%) were current users at the time of cancer diagnosis. Current antidepressant users had a 32% higher one-year mortality (MRR = 1.32, 95% CI: 1.29-1.35) and a 22% higher conditional five-year mortality (MRR = 1.22, 95% CI: 1.17-1.26) if patients survived the first year after the cancer diagnosis than patients not redeeming antidepressants. The one-year mortality was particularly high for patients who initiated antidepressant treatment within four months before cancer diagnosis (MRR = 1.54, 95% CI: 1.47-1.61). Former users had no increased cancer mortality. Initiation of antidepressive treatment prior to cancer diagnosis is common and is associated with an increased mortality.

  16. [Study of a beta-adrenergic stimulant and its antidepressant activity in man].

    PubMed

    Jouvent, R; Lecrubier, Y; Puech, A J; Simon, H F; Widlocher, D

    1977-01-01

    In animals, the psychopharmacological profile of beta-adrenergic stimulants is very similar to that of tricyclic antidepressants. In patients, more particularly in endogenous depressive patients, the antidepressant effect of salbutamol was very clear. A definite improvement was observed in all of the 22 studied patients after 1 to 3 days of intermittent venous infusion. The place of salbutamol in the therapeutic armamentarium of depressive states has still to be defined exactly. It is speculated that the antidepressant effect of imipramine-like derivatives is related to the stimulation of central beta 2-adrenergic receptors.

  17. Reviewing long-term antidepressants can reduce drug burden: a prospective observational cohort study

    PubMed Central

    Johnson, Chris F; Macdonald, Hector J; Atkinson, Pauline; Buchanan, Alasdair I; Downes, Noreen; Dougall, Nadine

    2012-01-01

    Background Antidepressant prescribing continues to rise. Contributing factors are increased long-term prescribing and possibly the use of higher selective serotonin re-uptake inhibitor (SSRI) doses. Aim To review general practice patients prescribed the same antidepressant long-term (≥2 years) and evaluate prescribing and management pre and post-review. Design and setting Prospective observational cohort study using routine data from 78 urban general practices, Scotland. Method All patients prescribed antidepressants (excluding amitriptyline) for ≥2 years were identified from records November 2009 to March 2010. GPs selected patients for face-to-face review of clinical condition and medication, December 2009 to September 2010. Pre- and post-review data were collected; average antidepressant doses and changes in prescribed daily doses were calculated. Onward referral to support services was recorded. Results 8.6% (33 312/388 656) of all registered patients were prescribed an antidepressant, 47.1% (15 689) were defined as long-term users and 2849 (18.2%) were reviewed. 811 (28.5%) patients reviewed had a change in antidepressant therapy: 7.0% stopped, 12.8% reduced dose, 5.3% increased dose, and 3.4% changed antidepressant, resulting in 9.5% (95% CI = 9.1% to 9.8% P<0.001) reduction in prescribed daily dose and 8.1% reduction in prescribing costs. 6.3% were referred onwards, half to NHS Mental Health Services. Pre-review SSRI doses were 10–30% higher than previously reported. Conclusion Almost half of all people prescribed antidepressants were long-term users. Appropriate reductions in prescribing can be achieved by reviewing patients. Higher SSRI doses may be contributing to current antidepressant growth. PMID:23211181

  18. Immunological studies on paroxetine, a novel anti-depressant drug.

    PubMed

    Henderson, D C; Edwards, R G; Weston, B J; Dewdney, J M

    1988-01-01

    Paroxetine is a novel and selective neuronal 5-hydroxy-tryptamine uptake inhibitor with anti-depressant activity. Paroxetine was examined for its ability to induce adverse immunological reactions, either as a consequence of a specific immune response or by a direct or indirect effect on the immune system. Paroxetine did not react in vitro with protein amino or thiol groups, suggesting that it lacks the capacity to form potentially immunogenic hapten protein conjugates. No anti-paroxetine antibody was detected in plasma or serum samples from patients and rats following oral administration over prolonged periods, or from epicutaneously exposed guinea pigs, or from rabbits given paroxetine in Freund's adjuvant, suggesting that paroxetine does not have the capacity to elicit humoral immune responses. Guinea pigs epicutaneously exposed to paroxetine did not develop contact sensitivity, suggesting that it does not have the capacity to elicit cell-mediated immune responses. These results suggest that paroxetine lacks intrinsic immunogenicity. Anti-SRBC antibody plaque-forming cell responses in mice were unaffected by oral administration of paroxetine, and paroxetine had no significant effect on ex vivo and in vitro murine macrophage phagocytosis of opsonized SRBC or on ex vivo murine splenocyte mitogen responses, suggesting that paroxetine does not exert modulatory effects on the immune system or on macrophage function. These findings, together with the results of pre-clinical safety evaluation studies, suggest that paroxetine is unlikely to have immunotoxic effects.

  19. Antidepressant monotherapy compared with combinations of antidepressants in the treatment of resistant depressive patients: a randomized, open-label study.

    PubMed

    Bares, Martin; Novak, Tomas; Kopecek, Miloslav; Stopkova, Pavla; Cermak, Jan; Kozeny, Jiri; Höschl, Cyril

    2013-02-01

    This randomized, 6-week, open-label study compared efficacy of CAD and antidepressant monotherapies (ADM) that had been chosen according to clinical judgment of the attending psychiatrist. A total of 60 inpatients (intent-to-treat analysis) with depressive disorder (≥ 1 unsuccessful antidepressant treatment) were randomly assigned to the interventions. The responders who completed the acute phase of study, were evaluated for relapse within 2 months of follow-up treatment. The primary outcome measure was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) and response was defined as a ≥ 50% reduction of MADRS score. Mean changes in total MADRS score from baseline to week 6 for patients in both treatment modalities were not different (ADM = 13.2 ± 8.6 points; CAD = 14.5 ± 9.5 points; P = 0.58). The analysis of covariance performed for significantly higher value of imipramine equivalent dose in CAD group showed only a non-significant between-group difference for total MADRS change (P = 0.17). There were also no differences between groups in response rate (ADM = 48%; CAD = 58%) and number of drop-outs in acute treatment as well as proportion of responders' relapses in the follow-up. Both treatment modalities produced clinically relevant reduction of depressive symptomatology in acute treatment of patients with resistant depression and their effect was comparable.

  20. Depression, antidepressants, and falls among community-dwelling elderly people: the MOBILIZE Boston study.

    PubMed

    Quach, Lien; Yang, Frances M; Berry, Sarah D; Newton, Elizabeth; Jones, Richard N; Burr, Jeffrey A; Lipsitz, Lewis A

    2013-12-01

    The mechanisms linking falls and depression are still unknown. The aim of the study is to examine the association between depression and antidepressants, with indoor and outdoor falls, and to investigate how antidepressants mediate this relationship. The study included 763 men and women aged 70 and older with baseline measures for depression and antidepressant use are captured with prospective data on falls from the "Maintenance of Balance, Independent Living, Intellect and Zest in the Elderly" (MOBILIZE) Boston study, which is a population-based longitudinal study (from 2005 to 2009). Overall, the rate of falls was 26 falls/100 person-years. Seventeen percent of participants had clinically significant depressive symptoms (CSDS), and 12% used antidepressants. CSDS increased the risk of indoor and outdoor falls (incidence rate ratio [IRR] = 1.6, 95% confidence interval [CI] = 1.2-2.3, p < .01; IRR = 1.6, 95% CI = 1.2-2.2, p < .01). Antidepressant use increased the risk of outdoor falls by 70% and partially mediated the association between CSDS and outdoor falls (IRR = 1.7, 95% CI = 1.2-2.5, p < .05). There was no relationship between antidepressant use and indoor falls. Similar results were observed when depression was considered as a continuous variable. Depression increased the risk of indoor and outdoor falls. Antidepressant use among older adults with CSDS increased the risk of outdoor, but not indoor falls. Clinicians should carefully consider the role of antidepressants among older adults with CSDS and their potential increase for the risk of outdoor falls.

  1. Depression, Antidepressants, and Falls Among Community-Dwelling Elderly People: The MOBILIZE Boston Study

    PubMed Central

    2013-01-01

    Background. The mechanisms linking falls and depression are still unknown. The aim of the study is to examine the association between depression and antidepressants, with indoor and outdoor falls, and to investigate how antidepressants mediate this relationship. Methods. The study included 763 men and women aged 70 and older with baseline measures for depression and antidepressant use are captured with prospective data on falls from the “Maintenance of Balance, Independent Living, Intellect and Zest in the Elderly” (MOBILIZE) Boston study, which is a population-based longitudinal study (from 2005 to 2009). Results. Overall, the rate of falls was 26 falls/100 person-years. Seventeen percent of participants had clinically significant depressive symptoms (CSDS), and 12% used antidepressants. CSDS increased the risk of indoor and outdoor falls (incidence rate ratio [IRR] = 1.6, 95% confidence interval [CI] = 1.2–2.3, p < .01; IRR = 1.6, 95% CI = 1.2–2.2, p < .01). Antidepressant use increased the risk of outdoor falls by 70% and partially mediated the association between CSDS and outdoor falls (IRR = 1.7, 95% CI = 1.2–2.5, p < .05). There was no relationship between antidepressant use and indoor falls. Similar results were observed when depression was considered as a continuous variable. Conclusions. Depression increased the risk of indoor and outdoor falls. Antidepressant use among older adults with CSDS increased the risk of outdoor, but not indoor falls. Clinicians should carefully consider the role of antidepressants among older adults with CSDS and their potential increase for the risk of outdoor falls. PMID:23817088

  2. Neurotrophin Genes and Antidepressant-Worsening Suicidal Ideation: A Prospective Case-Control Study

    PubMed Central

    Ramoz, Nicolas; Shekhtman, Tatyana; Courtet, Philippe; Gorwood, Philip; Kelsoe, John R.

    2016-01-01

    Background: Antidepressant-worsening suicidal ideation is a rare but serious phenomenon. This study aimed to test for association between antidepressant-worsening suicidal ideation and polymorphisms of BDNF/NTRK2 neurotrophin pathway genes, known to be involved in depression and suicide. Methods: This was a case-control study comparing patients with antidepressant-worsening suicidal ideation to patients without. Patients were collected from the GENESE cohort (3771 depressed tianeptine-treated outpatients). Antidepressant-worsening suicidal ideation was defined by an increase of at least 2 points on the Montgomery-Åsberg Depression Rating Scale-item10 during treatment. Controls were matched for age, sex, and baseline Montgomery-Åsberg Depression Rating Scale-item10 score. Thirteen single nucleotide polymorphisms covering 5 BDNF/NTRK2 pathway genes were genotyped. Results: A total 78 cases and 312 controls were included. Two NTRK2 single nucleotide polymorphisms were associated to antidepressant-worsening suicidal ideation: rs1439050 (P=.01) and rs1867283 (P=.04). Association with rs1439050 remained significant after adjustment for potentially confounding factors, including previous suicide attempts (P<.01). Conclusions: This naturalistic prospective study is consistent with previous studies on highlighting the potential role of the neurotrophin pathway, and especially of NTRK2, in antidepressant-worsening suicidal ideation. PMID:27378793

  3. Study of antidepressant drugs in GPR39 (zinc receptor⁻/⁻) knockout mice, showing no effect of conventional antidepressants, but effectiveness of NMDA antagonists.

    PubMed

    Młyniec, Katarzyna; Gaweł, Magdalena; Nowak, Gabriel

    2015-01-01

    The monoamine-based antidepressants that are currently used generate many side effects, and more than 30% of depressed patients do not respond to this therapy. Glutamate-based antidepressants seem to play an important role in therapy for depression, but there is still an extensive search for safe drugs. An antagonist of the glutamatergic NMDA receptor - namely, zinc - plays a part in maintaining homeostasis between glutamate and GABA via the GPR39 receptor, which has been found to be involved in the pathophysiology of depression. In this study we investigated the behavioral response resulting from chronic or acute treatment with monoamine-based antidepressants, such as imipramine, escitalopram or reboxetine, and from glutamate-based MK-801 or ketamine, as measured by the forced swim test (FST) in GPR39 knockout (GPR39 KO, -/-) mice versus wild-type (WT, +/+) controls. All the tested agents reduced the immobility time in the FST in the wild-type animals. However, only chronic or acute administration of MK-801 and ketamine (but not monoamine-based antidepressants) were active in the FST in GPR39 KO mice. Our results show for the first time that GPR39 is required for the antidepressant effect of monoamine-based antidepressants. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Antidepressant response to aripiprazole augmentation associated with enhanced FDOPA utilization in striatum: a preliminary PET study

    PubMed Central

    Conway, Charles R.; Chibnall, John T.; Cumming, Paul; Mintun, Mark A.; Gebara, Marie Anne I.; Perantie, Dana C.; Price, Joseph L.; Cornell, Martha E.; McConathy, Jonathan E.; Gangwani, Sunil; Sheline, Yvette I.

    2014-01-01

    Several double blind, prospective trials have demonstrated an antidepressant augmentation efficacy of aripiprazole in depressed patients unresponsive to standard antidepressant therapy. Although aripiprazole is now widely used for this indication, and much is known about its receptor-binding properties, the mechanism of its antidepressant augmentation remains ill-defined. In vivo animal studies and in vitro human studies using cloned dopamine dopamine D2 receptors suggest aripiprazole is a partial dopamine agonist; in this preliminary neuroimaging trial, we hypothesized that aripiprazole’s antidepressant augmentation efficacy arises from dopamine partial agonist activity. To test this, we assessed the effects of aripiprazole augmentation on the cerebral utilization of 6-[18F]-fluoro-3,4-dihydroxy-L-phenylalanine (FDOPA) using positron emission tomography (PET). Fourteen depressed patients, who had failed 8 weeks of antidepressant therapy with selective serotonin reuptake inhibitors, underwent FDOPA PET scans before and after aripiprazole augmentation; eleven responded to augmentation. Whole brain, voxel-wise comparisons of pre- and post-aripiprazole scans revealed increased FDOPA trapping in the right medial caudate of augmentation responders. An exploratory analysis of depressive symptoms revealed that responders experienced large improvements only in putatively dopaminergic symptoms of lassitude and inability to feel. These preliminary findings suggest that augmentation of antidepressant response by aripiprazole may be associated with potentiation of dopaminergic activity. PMID:24468015

  5. Antidepressant response to aripiprazole augmentation associated with enhanced FDOPA utilization in striatum: a preliminary PET study.

    PubMed

    Conway, Charles R; Chibnall, John T; Cumming, Paul; Mintun, Mark A; Gebara, Marie Anne I; Perantie, Dana C; Price, Joseph L; Cornell, Martha E; McConathy, Jonathan E; Gangwani, Sunil; Sheline, Yvette I

    2014-03-30

    Several double blind, prospective trials have demonstrated an antidepressant augmentation efficacy of aripiprazole in depressed patients unresponsive to standard antidepressant therapy. Although aripiprazole is now widely used for this indication, and much is known about its receptor-binding properties, the mechanism of its antidepressant augmentation remains ill-defined. In vivo animal studies and in vitro human studies using cloned dopamine dopamine D2 receptors suggest aripiprazole is a partial dopamine agonist; in this preliminary neuroimaging trial, we hypothesized that aripiprazole's antidepressant augmentation efficacy arises from dopamine partial agonist activity. To test this, we assessed the effects of aripiprazole augmentation on the cerebral utilization of 6-[(18)F]-fluoro-3,4-dihydroxy-l-phenylalanine (FDOPA) using positron emission tomography (PET). Fourteen depressed patients, who had failed 8 weeks of antidepressant therapy with selective serotonin reuptake inhibitors, underwent FDOPA PET scans before and after aripiprazole augmentation; 11 responded to augmentation. Whole brain, voxel-wise comparisons of pre- and post-aripiprazole scans revealed increased FDOPA trapping in the right medial caudate of augmentation responders. An exploratory analysis of depressive symptoms revealed that responders experienced large improvements only in putatively dopaminergic symptoms of lassitude and inability to feel. These preliminary findings suggest that augmentation of antidepressant response by aripiprazole may be associated with potentiation of dopaminergic activity. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. Antidepressant Efficacy for Depression in Children and Adolescents: Industry- and NIMH-Funded Studies.

    PubMed

    Walkup, John T

    2017-05-01

    Significant controversy surrounds the efficacy of the newer antidepressants for children and adolescents with depression. The controversy largely hinges on meta-analyses of studies that suggest that antidepressants are minimally effective, not effective, or equivalent to placebo. In this review, the author discusses several scientific and clinical complexities that are important to understand in reviewing the antidepressant literature: the strengths and weaknesses of meta-analyses; the scientific and regulatory context for the large number of antidepressant trials in the late 1990s and early 2000s; and the distinction between a negative trial, where the treatment does not demonstrate efficacy, and a failed trial, where methodological problems make it impossible to draw any conclusion about efficacy. It is the premise of this review that meta-analyses that include the large number of industry-sponsored antidepressant trials distort the picture of antidepressant efficacy for teen depression. Industry-sponsored child and adolescent depression trials suffer from a number of implementation challenges and should be considered failed trials that are largely uninformative and not eligible to be included in efficacy meta-analyses. In contrast to the industry-sponsored trials, depression trials funded by the National Institute of Mental Health (NIMH) (N=2) are characterized by many methodological strengths, lower placebo response rates (30%-35%), and meaningful between-group differences (25%-30%) that support antidepressant efficacy. The NIMH-funded trials, taken together with the demonstrated efficacy of the serotonin reuptake inhibitors for childhood-onset obsessive-compulsive disorder and the anxiety disorders, suggest a broad and important role for antidepressant medications in pediatric internalizing conditions.

  7. Brain arousal regulation as response predictor for antidepressant therapy in major depression

    PubMed Central

    Schmidt, Frank M.; Sander, Christian; Dietz, Marie-Elisa; Nowak, Claudia; Schröder, Thomas; Mergl, Roland; Schönknecht, Peter; Himmerich, Hubertus; Hegerl, Ulrich

    2017-01-01

    A tonically high level of brain arousal and its hyperstable regulation is supposed to be a pathogenic factor in major depression. Preclinical studies indicate that most antidepressants may counteract this dysregulation. Therefore, it was hypothesized that responders to antidepressants show a) a high level of EEG-vigilance (an indicator of brain arousal) and b) a more stable EEG-vigilance regulation than non-responders. In 65 unmedicated depressed patients 15-min resting-state EEGs were recorded off medication (baseline). In 57 patients an additional EEG was recorded 14 ± 1 days following onset of antidepressant treatment (T1). Response was defined as a ≥50% HAMD-17-improvement after 28 ± 1 days of treatment (T2), resulting in 29 responders and 36 non-responders. Brain arousal was assessed using the Vigilance Algorithm Leipzig (VIGALL 2.1). At baseline responders and non-responders differed in distribution of overall EEG-vigilance stages (F2,133 = 4.780, p = 0.009), with responders showing significantly more high vigilance stage A and less low vigilance stage B. The 15-minutes Time-course of EEG-vigilance did not differ significantly between groups. Exploratory analyses revealed that responders showed a stronger decline in EEG-vigilance levels from baseline to T1 than non-responders (F2,130 = 4.978, p = 0.005). Higher brain arousal level in responders to antidepressants supports the concept that dysregulation of brain arousal is a possible predictor of treatment response in affective disorders. PMID:28345662

  8. Penile Low Intensity Shock Wave Treatment is Able to Shift PDE5i Nonresponders to Responders: A Double-Blind, Sham Controlled Study.

    PubMed

    Kitrey, Noam D; Gruenwald, Ilan; Appel, Boaz; Shechter, Arik; Massarwa, Omar; Vardi, Yoram

    2016-05-01

    We performed sham controlled evaluation of penile low intensity shock wave treatment effect in patients unable to achieve sexual intercourse using PDE5i (phosphodiesterase type 5 inhibitor). This prospective, randomized, double-blind, sham controlled study was done in patients with vasculogenic erectile dysfunction who stopped using PDE5i due to no efficacy. All patients had an erection hardness score of 2 or less with PDE5i. A total of 58 patients were randomized, including 37 treated with low intensity shock waves (12 sessions of 1,500 pulses of 0.09 mJ/mm(2) at 120 shock waves per minute) and 18 treated with a sham probe. In the sham group 16 patients underwent low intensity shock wave treatment 1 month after sham treatment. All patients were evaluated at baseline and 1 month after the end of treatment using validated erectile dysfunction questionnaires and the flow mediated dilatation technique for penile endothelial function. Erectile function was evaluated while patients were receiving PDE5i. In the low intensity shock wave treatment group and the sham group 54.1% and 0% of patients, respectively, achieved erection hard enough for vaginal penetration, that is an EHS (Erection Hardness Score) of 3 (p <0.0001). According to changes in the IIEF-EF (International Index of Erectile Function-Erectile Function) score treatment was effective in 40.5% of men who received low intensity shock wave treatment but in none in the sham group (p = 0.001). Of patients treated with shock waves after sham treatment 56.3% achieved erection hard enough for penetration (p <0.005). Low intensity shock wave treatment is effective even in patients with severe erectile dysfunction who are PDE5i nonresponders. After treatment about half of them were able to achieve erection hard enough for penetration with PDE5i. Longer followup is needed to establish the place of low intensity shock wave treatment in these challenging cases. Copyright © 2016 American Urological Association Education

  9. Antidepressants during pregnancy and autism in offspring: population based cohort study.

    PubMed

    Rai, Dheeraj; Lee, Brian K; Dalman, Christina; Newschaffer, Craig; Lewis, Glyn; Magnusson, Cecilia

    2017-07-19

    Objectives To study the association between maternal use of antidepressants during pregnancy and autism spectrum disorder (ASD) in offspring.Design Observational prospective cohort study with regression methods, propensity score matching, sibling controls, and negative control comparison.Setting Stockholm County, Sweden.Participants 254 610 individuals aged 4-17, including 5378 with autism, living in Stockholm County in 2001-11 who were born to mothers who did not take antidepressants and did not have any psychiatric disorder, mothers who took antidepressants during pregnancy, or mothers with psychiatric disorders who did not take antidepressants during pregnancy. Maternal antidepressant use was recorded during first antenatal interview or determined from prescription records.Main outcome measure Offspring diagnosis of autism spectrum disorder, with and without intellectual disability.Results Of the 3342 children exposed to antidepressants during pregnancy, 4.1% (n=136) had a diagnosis of autism compared with a 2.9% prevalence (n=353) in 12 325 children not exposed to antidepressants whose mothers had a history of a psychiatric disorder (adjusted odds ratio 1.45, 95% confidence interval 1.13 to 1.85). Propensity score analysis led to similar results. The results of a sibling control analysis were in the same direction, although with wider confidence intervals. In a negative control comparison, there was no evidence of any increased risk of autism in children whose fathers were prescribed antidepressants during the mothers' pregnancy (1.13, 0.68 to 1.88). In all analyses, the risk increase concerned only autism without intellectual disability.Conclusions The association between antidepressant use during pregnancy and autism, particularly autism without intellectual disability, might not solely be a byproduct of confounding. Study of the potential underlying biological mechanisms could help the understanding of modifiable mechanisms in the aetiology of

  10. Relationship of pharmaceutical promotion to antidepressant switching and adherence: a retrospective cohort study.

    PubMed

    Hansen, Richard A; Chen, Shih-Yin; Gaynes, Bradley N; Maciejewski, Matthew L

    2010-12-01

    Patient nonadherence and early discontinuation of antidepressant treatment are common. Pharmaceutical promotion to consumers and physicians may influence this behavior. The objectives of this study were to explore whether promotional spending is related to early antidepressant switching, acute-phase adherence, and continuation-phase adherence. A retrospective cohort study was conducted with national promotional expenditure data merged with medical and prescription claims data from a large national health plan affiliated with i3 Innovus. Included were records for continuously insured adults with major depression who received a new prescription for an antidepressant: 5,010 were in the cohort assessed for switching, 4,457 were in the cohort assessed for acute-phase adherence, and 1,772 were in the cohort assessed for continuation-phase adherence. National promotional efforts were estimated by examining inflation-adjusted spending on direct-to-consumer advertising (DTCA) and physician detailing. Clinical guidelines were used to create proxies for aspects of treatment outcomes, including antidepressant switching and adherence in the acute phase and adherence in the continuation phase. Logistic regression models estimated the association between promotional variables and these outcomes. Patients taking medications that were more highly promoted to physicians were less likely to switch medications (odds ratio [OR]=.61) and were more likely to be adherent during the acute phase of treatment (OR=1.13). DTCA had little effect on switching or antidepressant adherence. Detailing to physicians was associated with lower rates of medication switching and had a positive relationship with patient adherence during early antidepressant treatment. This finding indicates that certain aspects of promotion may have beneficial effects on antidepressant use.

  11. Use of antidepressants and association with elective termination of pregnancy: population based case-control study.

    PubMed

    Kieler, H; Malm, H; Artama, M; Engeland, A; Furu, K; Gissler, M; Nørgaard, M; Stephansson, O; Valdimarsdottir, U; Zoega, H; Haglund, B

    2015-11-01

    To assess whether the use of selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, mirtazapine, venlafaxine or other antidepressants is associated with late elective termination of pregnancy. Case-control study using data from national registers. Denmark, Finland, and Norway during the period 1996-2007. A total of 14,902 women were included as cases and 148,929 women were included as controls. Cases were women with elective termination of pregnancy at 12-23 weeks of gestation. Controls continued their pregnancy and were matched with cases on key factors. Association between antidepressant use during pregnancy and elective termination of pregnancy at 12-23 weeks of gestation for fetal anomalies, or for maternal ill health or socio-economic disadvantage. At least one prescription of antidepressants was filled by 3.7% of the cases and 2.2% of the controls. Use of any type of antidepressant was associated with elective termination of pregnancy for maternal ill health or socio-economic disadvantage (odds ratio, OR 2.3; 95% confidence interval, 95% CI 2.0-2.5). Elective termination of pregnancy for fetal anomalies was associated with the use of mirtazapine (OR 2.2, 95% CI 1.1-4.5). There was no association between the use of any of the other antidepressants and elective termination of pregnancy for fetal anomalies. The use of any type of antidepressants was associated with elective termination of pregnancy at 12-23 weeks for maternal ill health or socio-economic disadvantage, but not with terminations for fetal anomalies. Further studies need to confirm the findings concerning mirtazapine and termination of pregnancy for fetal anomalies. © 2014 The Authors. BJOG An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.

  12. Brain effects of antidepressants in major depression: a meta-analysis of emotional processing studies.

    PubMed

    Delaveau, Pauline; Jabourian, Maritza; Lemogne, Cédric; Guionnet, Sophie; Bergouignan, Loretxu; Fossati, Philippe

    2011-04-01

    A consistent brain activity pattern has been identified in major depression across many resting positron emission tomography (PET) studies. This dysfunctional pattern seems to be normalized by antidepressant treatment. The aim of this meta-analysis was to identify more clearly the pattern associated with clinical improvement of depression following an antidepressant drug treatment, in emotional activation studies using functional magnetic resonance imaging (fMRI). A quantitative Activation Likelihood Estimation (ALE) meta-analysis was performed across 9 emotional activation fMRI and PET studies (126 patients) using the Activation Likelihood Estimation technique. Following the antidepressant drug treatment, the activation of dorsolateral, dorsomedial and ventrolateral prefrontal cortices was increased whereas the activation of the amygdala, hippocampus, parahippocampal region, ventral anterior cingulate cortex, orbitofrontal cortex, and insula was decreased. Additionally, there was a decreased activation in the anterior (BA 32) and posterior cingulate cortices, as well as in the precuneus and inferior parietal lobule, which could reflect a restored deactivation of the default mode network. The small number of emotional activation studies, using heterogeneous tasks, included in the ALE analysis. The activation of several brain regions involved in major depression, in response to emotional stimuli, was normalized after antidepressant treatment. To refine our knowledge of antidepressants' effect on the neural bases of emotional processing in major depression, neuroimaging studies should use consistent emotional tasks related to depressive symptoms and that involve the default mode network, such as self-referential processing tasks. Copyright © 2010 Elsevier B.V. All rights reserved.

  13. Neurobiology of mood, anxiety, and emotions as revealed by studies of a unique antidepressant: tianeptine.

    PubMed

    McEwen, B S; Olié, J P

    2005-06-01

    Recent studies have provided evidence that structural remodeling of certain brain regions is a feature of depressive illness, and the postulated underlying mechanisms contribute to the idea that there is more to antidepressant actions that can be explained exclusively by a monoaminergic hypothesis. This review summarizes recent neurobiological studies on the antidepressant, tianeptine (S-1574, [3-chloro-6-methyl-5,5-dioxo-6,11-dihydro-(c,f)-dibenzo-(1,2-thiazepine)-11-yl) amino]-7 heptanoic acid, sodium salt), a compound with structural similarities to the tricyclic antidepressant agents, the efficacy and good tolerance of which have been clearly established. These studies have revealed that the neurobiological properties of tianeptine involve the dynamic interplay between numerous neurotransmitter systems, as well as a critical role of structural and functional plasticity in the brain regions that permit the full expression of emotional learning. Although the story is far from complete, the schema underlying the effect of tianeptine on central plasticity is the most thoroughly studied of any antidepressants. Effects of tianeptine on neuronal excitability, neuroprotection, anxiety, and memory have also been found. Together with clinical data on the efficacy of tianeptine as an antidepressant, these actions offer insights into how compounds like tianeptine may be useful in the treatment of neurobiological features of depressive disorders.

  14. Disproportionate Reduction of Serotonin Transporter May Predict the Response and Adherence to Antidepressants in Patients with Major Depressive Disorder: A Positron Emission Tomography Study with 4-[18F]-ADAM.

    PubMed

    Yeh, Yi-Wei; Ho, Pei-Shen; Kuo, Shin-Chang; Chen, Chun-Yen; Liang, Chih-Sung; Yen, Che-Hung; Huang, Chang-Chih; Ma, Kuo-Hsing; Shiue, Chyng-Yann; Huang, Wen-Sheng; Shyu, Jia-Fwu; Wan, Fang-Jung; Lu, Ru-Band; Huang, San-Yuan

    2015-01-07

    Many lines of evidence suggest the role of serotonin transporter (SERT)-mediated reuptake of serotonin in the pathophysiology and treatment of major depressive disorder (MDD). This study aimed to examine whether the pretreatment of SERT binding potential or SERT binding ratio between terminal projection regions relative to the midbrain raphe nuclei was associated with treatment outcomes to SERT-targeted antidepressants. We recruited 39 antidepressant-naïve patients with MDD and 39 heathy controls. Positron emission tomography with N,N-dimethyl-2-(2-amino-4-[(18)F]fluorophenylthio)benzylamine (4-[(18)F]-ADAM) was used to measure in vivo SERT availability prior to antidepressant treatment. The 21-item Hamilton Depression Rating Scale (HDRS) was use to assess the severity of depression from baseline to week 6. All the patients with MDD had HDRS scores of 18 or more. Pretreatment SERT binding in the thalamus and striatum positively correlated with an early reduction in HDRS scores at week 3. Nonresponders and dropout patients showed a proportionate reduction in SERT binding in the terminal projection regions and midbrain compared to healthy controls. In contrast, a disproportionate reduction in SERT binding in the terminal projection regions relative to midbrain was observed in responders. The results of this study suggested that a disproportionate reduction in SERT binding between terminal projection regions and midbrain may predict better treatment outcomes in patients with MDD. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  15. Do Antidepressants Lower the Prevalence of Lithium-associated Hypernatremia in the Elderly? A Retrospective Study

    PubMed Central

    Rej, Soham; Looper, Karl; Segal, Marilyn

    2013-01-01

    Background Clinically important measures of lithium-induced nephrogenic diabetes insipidus (NDI) such as hypernatremia have not been well-studied. This is especially relevant for the elderly who, in comparison to younger adults, may become symptomatic and require hospitalization with relatively small elevations in sodium levels. We hypothesized that antidepressant use, which has been associated with the syndrome of inappropriate antidiuretic hormone secretion, has a protective effect against lithium-associated hypernatremia in the elderly. Methods Retrospective cohort study of 55 geriatric psychiatry outpatients followed at tertiary-care hospitals. Patients using lithium and antidepressants were compared with those using lithium alone for prevalence rates of hypernatremia during a 15-year observational period. Results The prevalence of hypernatremia was less in patients who had concurrent use of lithium and antidepressants, as compared to lithium alone 3/35 (8.6%) vs. 8/20 (40%), OR 0.14, p = .011. Conclusions Our results suggest that elderly lithium patients are less likely to develop hypernatremia if they are taking antidepressants concurrently. Whether antidepressants may be useful in the prevention of lithium-associated hypernatremia should be assessed in future prospective observational or treatment studies. PMID:23737927

  16. Antidepressant use and lifetime history of mental disorders in a community sample: results from the Baltimore Epidemiologic Catchment Area Study.

    PubMed

    Takayanagi, Yoichiro; Spira, Adam P; Bienvenu, O Joseph; Hock, Rebecca S; Carras, Michelle C; Eaton, William W; Mojtabai, Ramin

    2015-01-01

    Past studies have shown that many individuals who use antidepressants have no current or lifetime history of mental disorders. However, recent studies suggest that the one-time retrospective evaluation of mental disorders commonly used in such studies may substantially underestimate the true lifetime prevalence of mental disorders. We examined the prevalence of mental disorders, assessed prospectively over multiple interviews, among individuals currently using antidepressants in a community sample. Using data from the Baltimore Epidemiologic Catchment Area (ECA) Study Wave 1 (1981) through Wave 4 (2004-2005) (N = 1,071), we assessed lifetime prevalence of common mood and anxiety disorders according to DSM-III and DSM-III-R criteria, based on 4 interviews, among participants who reported current antidepressant use. Furthermore, we examined factors associated with current antidepressant use. Thirteen percent of participants at Wave 4 reported currently using antidepressant medications. Among antidepressant users, 69% never met criteria for major depressive disorder (MDD); and 38% never met criteria for MDD, obsessive-compulsive disorder, panic disorder, social phobia, or generalized anxiety disorder in their lifetime. Female gender, Caucasian ethnicity, recent or current physical problems (eg, loss of bladder control, hypertension, and back pain), and recent mental health facility visits were associated with antidepressant use in addition to mental disorders. Many individuals who are prescribed and use antidepressant medications may not have met criteria for mental disorders. Our data indicate that antidepressants are commonly used in the absence of clear evidence-based indications. © Copyright 2015 Physicians Postgraduate Press, Inc.

  17. Cancer Mortality in People Treated with Antidepressants before Cancer Diagnosis: A Population Based Cohort Study

    PubMed Central

    Sun, Yuelian; Vedsted, Peter; Fenger-Grøn, Morten; Wu, Chun Sen; Bech, Bodil Hammer; Olsen, Jørn; Benros, Michael Eriksen; Vestergaard, Mogens

    2015-01-01

    Background Depression is common after a cancer diagnosis and is associated with an increased mortality, but it is unclear whether depression occurring before the cancer diagnosis affects cancer mortality. We aimed to study cancer mortality of people treated with antidepressants before cancer diagnosis. Methods and Findings We conducted a population based cohort study of all adults diagnosed with cancer between January 2003 and December 2010 in Denmark (N = 201,662). We obtained information on cancer from the Danish Cancer Registry, on the day of death from the Danish Civil Registry, and on redeemed antidepressants from the Danish National Prescription Registry. Current users of antidepressants were defined as those who redeemed the latest prescription of antidepressant 0–4 months before cancer diagnosis (irrespective of earlier prescriptions), and former users as those who redeemed the latest prescription five or more months before cancer diagnosis. We estimated an all-cause one-year mortality rate ratio (MRR) and a conditional five-year MRR for patients who survived the first year after cancer diagnosis and confidence interval (CI) using a Cox proportional hazards regression model. Overall, 33,111 (16.4%) patients redeemed at least one antidepressant prescription in the three years before cancer diagnosis of whom 21,851 (10.8%) were current users at the time of cancer diagnosis. Current antidepressant users had a 32% higher one-year mortality (MRR = 1.32, 95% CI: 1.29–1.35) and a 22% higher conditional five-year mortality (MRR = 1.22, 95% CI: 1.17–1.26) if patients survived the first year after the cancer diagnosis than patients not redeeming antidepressants. The one-year mortality was particularly high for patients who initiated antidepressant treatment within four months before cancer diagnosis (MRR = 1.54, 95% CI: 1.47–1.61). Former users had no increased cancer mortality. Conclusions Initiation of antidepressive treatment prior to cancer diagnosis is

  18. Antidepressant Use and Lifetime History of Mental Disorders in a Community Sample: Results from the Baltimore Epidemiologic Catchment Area Study

    PubMed Central

    Takayanagi, Yoichiro; Spira, Adam P.; Bienvenu, O. Joseph; Hock, Rebecca S.; Carras, Michelle C.; Eaton, William W.; Mojtabai, Ramin

    2015-01-01

    Objectives Past studies have shown that many individuals who use antidepressants do not have a current or lifetime history of mental disorders. However, recent studies suggest that the one-time retrospective evaluation of mental disorders commonly used in such studies may substantially underestimate the true lifetime prevalence of mental disorders. We examined the prevalence of mental disorders, assessed prospectively over multiple interviews, among individuals currently using antidepressants in a community sample. Methods Using data from the Baltimore Epidemiologic Catchment Area (ECA) Survey Wave 1 (1981) through Wave 4 (2004) (N = 1071), we assessed lifetime prevalence of common mood and anxiety disorders according to the DSM-III and DSM-III-R criteria, based on 4 interviews, among participants who reported current antidepressant use. Furthermore, we examined factors associated with current antidepressant use. Results Thirteen percent of participants at Wave 4 reported currently using antidepressant medications. Among antidepressant users, 69% never met criteria for major depressive disorder (MDD), and 38% never met criteria for MDD, obsessive-compulsive disorder, panic disorder, social phobia, or generalized anxiety disorder in their lifetime. Female gender, Caucasian ethnicity, recent or current physical problems (e.g., loss of bladder control, hypertension and back pain) and recent mental health facility visits were associated with antidepressant use in addition to mental disorders. Conclusions Many individuals who are prescribed and use antidepressant medications may not have met criteria for mental disorders. Our data indicate that antidepressants are commonly used in the absence of clear evidence-based indications. PMID:25188822

  19. Metabonomic study on the antidepressant-like effects of banxia houpu decoction and its action mechanism.

    PubMed

    Ma, Zhanqiang; Ji, Weiwei; Qu, Rong; Wang, Mingyan; Yang, Wen; Zhan, Zhen; Fu, Qiang; Ma, Shiping

    2013-01-01

    The aim of this study was to establish an experimental model for metabonomic profiles of the rat's brain and then to investigate the antidepressant effect of Banxia Houpu decoction (BHD) and its possible mechanisms. Behavioral research and metabonomics method based on UPLC-MS were used to assess the efficacy of different fractions of BHD on chronic unpredictable mild stress (CUMS) model of depression. There was a significant difference between the BHD group and the model group. Eight endogenous metabolites, which are contributing to the separation of the model group and control group, were detected, while BHD group regulated the perturbed metabolites showing that there is a tendency of recovery compared to control group. Therefore, we think that those potential metabolite biomarkers have some relationship with BHD's antidepression effect. This work appraised the antidepressant effect of Banxia Houpu decoction as well as revealing a metabonomics method, a valuable parameter in the TCM research.

  20. Metabonomic Study on the Antidepressant-Like Effects of Banxia Houpu Decoction and Its Action Mechanism

    PubMed Central

    Ji, Weiwei; Qu, Rong; Wang, Mingyan; Yang, Wen; Zhan, Zhen; Ma, Shiping

    2013-01-01

    The aim of this study was to establish an experimental model for metabonomic profiles of the rat's brain and then to investigate the antidepressant effect of Banxia Houpu decoction (BHD) and its possible mechanisms. Behavioral research and metabonomics method based on UPLC-MS were used to assess the efficacy of different fractions of BHD on chronic unpredictable mild stress (CUMS) model of depression. There was a significant difference between the BHD group and the model group. Eight endogenous metabolites, which are contributing to the separation of the model group and control group, were detected, while BHD group regulated the perturbed metabolites showing that there is a tendency of recovery compared to control group. Therefore, we think that those potential metabolite biomarkers have some relationship with BHD's antidepression effect. This work appraised the antidepressant effect of Banxia Houpu decoction as well as revealing a metabonomics method, a valuable parameter in the TCM research. PMID:24250712

  1. Evaluation of Overactive Bladder in Male Antidepressant Users: A Prospective Study

    PubMed Central

    2017-01-01

    Purpose In this study, we investigated overactive bladder (OAB) functions in male patients who used antidepressant drugs (ADs) that were previously examined in female patients, based on conflicting data in literature regarding the effects of AD on OAB and the differences between male and female urinary system physiologies (anatomical and hormonal). Methods The study included 202 male patients (a control group of 90 healthy subjects, and an experimental group of 112 patients taking ADs for different disorders). All the patients completed the overactive bladder-validated 8 (OAB-V8) questionnaire, the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), and the Beck Depression Inventory (BDS). Results The OAB-V8, ICIQ-SF, and BDS scores for the antidepressant users were significantly higher than those of the control group. The highest prevalence of OAB symptoms was observed in patients taking venlafaxine (68.2%), and the lowest prevalence was in patients taking sertraline (28.0%). Moreover, the frequency of OAB between the antidepressant groups was statistically significant. The univariate logistic regression analyses showed a significant relationship between the presence of OAB, antidepressant usage, BDS score, and the age of a patient. In the multivariate logistic regression analyses, the association between the presence of OAB and antidepressant usage was statistically significant. Conclusions The present study showed that the incidence of OAB and the severity of OAB symptoms increased in males using antidepressants for various disorders. This may have been due to unique pharmacological effects, on a molecular or individual level, of serotonin-norepinephrine reuptake inhibitors. PMID:28361516

  2. Antidepressants and risk of cataract development: A population-based, nested case-control study.

    PubMed

    Chou, Po-Han; Chu, Che-Sheng; Chen, Yi-Huei; Hsu, Min-Yen; Huang, Min-Wei; Lan, Tsuo-Hung; Lin, Ching-Heng

    2017-06-01

    Previous studies demonstrated increased risk of cataract development among users of selective serotonin reuptake inhibitors (SSRIs). However, it remains unknown whether this risk also prevails with the use of other types of antidepressants. The aim of this study was to investigate whether use of antidepressants is associated with an increased risk of cataract development. Moreover, the relationship between binding affinities of serotonin transporter (SERT) of antidepressant and the risk of cataracts is examined. We conducted a nested case-control study using National Health Insurance Research Database in Taiwan. A total of 14,288 patients were included; 7651 in the cataract group and 6637 in the control group. Antidepressant exposure was categorized by type, duration of use, and binding affinities of SERT. The association between antidepressant exposure and cataract development was assessed using conditional logistic regression analysis. The adjusted odds ratios (AORs) for developing cataracts among continuous users of SSRIs, serotonin norepinephrine reuptake inhibitors (SNRIs), and other antidepressants were 1.26 (95% confidence interval (CI): 1.12-1.41, p<0.001), 1.21 (95% CI: 1.02-1.43, p=0.027), and 1.18 (95% CI: 1.04-1.34, p=0.009) respectively. Specifically, continuous uses of fluoxetine (AOR: 1.21; 95% CI: 1.01-1.46, p=0.042), fluvoxamine (AOR: 1.47; 95% CI: 1.01-2.12, p=0.043), venlafaxine (AOR: 1.44; 95% CI: 1.19-1.74, p<0.001) significantly increased the risk of cataract development. Moreover, continuous users of antidepressants with intermediate SERT binding affinities (AOR: 1.68; 95% CI: 1.10-2.56, p=0.017) were significantly associated with increased risks of cataract development. Several confounding factors such as obesity, multiple drug users, family history of cataracts, substance use, and environmental factors (such as sunlight or radiation exposure) were acquired. We found increased risk of cataract development in patients continuously using

  3. Effects of Antidepressants, but not Psychopathology, on Cardiac Sympathetic Control: A Longitudinal Study

    PubMed Central

    Licht, Carmilla M M; Penninx, Brenda W J H; de Geus, Eco J C

    2012-01-01

    Increased sympathetic activity has been hypothesized to have a role in the elevated somatic disease risk in persons with depressive or anxiety disorders. However, it remains unclear whether increased sympathetic activity reflects a direct effect of anxiety or depression or an indirect effect of antidepressant medication. The aim of this study was to test longitudinally whether cardiac sympathetic control, measured by pre-ejection period (PEP), was increased by depression/anxiety status and by antidepressant use. Cross-sectional and longitudinal data were from a depression and anxiety cohort: the Netherlands Study of Depression and Anxiety (NESDA). Baseline data of 2838 NESDA subjects (mean age 41.7 years, 66.7% female) and 2-year follow-up data of 2226 subjects were available for analyses. Included were subjects with and without depressive/anxiety disorders, using or not using different antidepressants at baseline or follow-up. The PEP was measured non-invasively by 1.5 h of ambulatory impedance cardiography. Cross-sectional analyses compared PEP across psychopathology and antidepressant groups. Longitudinal analyses compared 2-year changes in PEP in relation to changes in psychopathology and antidepressant use. Cross-sectional analyses showed that antidepressant-naïve depressive/anxious subjects had comparable PEP as controls, whereas subjects using tricyclic (TCA) or combined serotonergic/noradrenergic antidepressants (SNRI) had significantly shorter PEP compared with controls. In contrast, subjects using selective serotonin re-uptake inhibitors (SSRIs) had longer PEP than controls. Longitudinal results confirmed these findings: compared with 2-year change in PEP in continuous non-users (+2 ms), subjects who started TCA or SNRI treatment showed significantly shortened PEP (−11 ms, p=0.005 and p<0.001), whereas subjects who started SSRI treatment showed significant prolongation of PEP (+9 ms, p=0.002). Reversed findings were observed among those who

  4. Effects of antidepressants, but not psychopathology, on cardiac sympathetic control: a longitudinal study.

    PubMed

    Licht, Carmilla M M; Penninx, Brenda W J H; de Geus, Eco J C

    2012-10-01

    Increased sympathetic activity has been hypothesized to have a role in the elevated somatic disease risk in persons with depressive or anxiety disorders. However, it remains unclear whether increased sympathetic activity reflects a direct effect of anxiety or depression or an indirect effect of antidepressant medication. The aim of this study was to test longitudinally whether cardiac sympathetic control, measured by pre-ejection period (PEP), was increased by depression/anxiety status and by antidepressant use. Cross-sectional and longitudinal data were from a depression and anxiety cohort: the Netherlands Study of Depression and Anxiety (NESDA). Baseline data of 2838 NESDA subjects (mean age 41.7 years, 66.7% female) and 2-year follow-up data of 2226 subjects were available for analyses. Included were subjects with and without depressive/anxiety disorders, using or not using different antidepressants at baseline or follow-up. The PEP was measured non-invasively by 1.5 h of ambulatory impedance cardiography. Cross-sectional analyses compared PEP across psychopathology and antidepressant groups. Longitudinal analyses compared 2-year changes in PEP in relation to changes in psychopathology and antidepressant use. Cross-sectional analyses showed that antidepressant-naïve depressive/anxious subjects had comparable PEP as controls, whereas subjects using tricyclic (TCA) or combined serotonergic/noradrenergic antidepressants (SNRI) had significantly shorter PEP compared with controls. In contrast, subjects using selective serotonin re-uptake inhibitors (SSRIs) had longer PEP than controls. Longitudinal results confirmed these findings: compared with 2-year change in PEP in continuous non-users (+2 ms), subjects who started TCA or SNRI treatment showed significantly shortened PEP (-11 ms, p=0.005 and p<0.001), whereas subjects who started SSRI treatment showed significant prolongation of PEP (+9 ms, p=0.002). Reversed findings were observed among those who

  5. The relationship between socio-economic status and antidepressant prescription: a longitudinal survey and register study of young adults.

    PubMed

    von Soest, T; Bramness, J G; Pedersen, W; Wichstrøm, L

    2012-03-01

    The current study examines the relationship between socio-economic status (SES) and antidepressant prescription among young adults and investigates mechanisms that could explain such a potential social gradient. Longitudinal survey data from a population-based Norwegian sample (N = 2606) was collected in four waves over a 13-year period. The data were linked to register data on antidepressant prescription and several indicators of SES (education, income, social or unemployment benefits, disability or rehabilitation benefits and parents' education). Apart from parents' education, all indicators of low SES were related to higher rates of antidepressant prescription. A part of the relationship between SES and antidepressant prescription was due to low SES being related to higher levels of anxiety and depression. Moreover, low SES was related to more frequent use of mental health services, which again was related to higher rates of antidepressant prescription. Both contact with physicians and other mental healthcare professionals accounted for some of the relationship between SES and antidepressant prescription. The study provides information about mechanisms involved in the relationship between low SES and antidepressant prescription. More research is needed about whether a comparable social gradient in antidepressant prescription is also to be found outside the Nordic countries.

  6. Antidepressant effect on connectivity of the mood-regulating circuit: an FMRI study.

    PubMed

    Anand, Amit; Li, Yu; Wang, Yang; Wu, Jingwei; Gao, Sujuan; Bukhari, Lubna; Mathews, Vincent P; Kalnin, Andrew; Lowe, Mark J

    2005-07-01

    The mechanisms by which antidepressant-induced neurochemical changes lead to physiological changes in brain circuitry and ultimately an antidepressant response remain unclear. This study investigated the effects of sertraline, a selective serotonin reuptake inhibitor antidepressant, on corticolimbic connectivity, using functional magnetic resonance imaging (fMRI). In all, 12 unmedicated unipolar depressed patients and 11 closely matched healthy control subjects completed two fMRI scanning sessions at baseline and after 6 weeks. Depressed patients received treatment with sertraline between the two sessions. During each fMRI session, subjects first completed a conventional block-design experiment. Next, connectivity between cortical and limbic regions was measured using correlations of low-frequency blood oxygen level-dependent (BOLD) fluctuations (LFBF) during continuous exposure to neutral, positive, and negative pictures. At baseline, depressed patients had decreased corticolimbic LFBF correlations compared to healthy subjects during the resting state and on exposure to emotionally valenced pictures. At rest and on exposure to neutral and positive pictures, LFBF correlation between the anterior cingulate cortex and limbic regions was significantly increased in patients after treatment. However, on exposure to negative pictures, corticolimbic LFBF correlations remained decreased in depressed patients. The results of this study are consistent with the hypothesis that antidepressant treatment may increase corticolimbic connectivity, thereby possibly increasing the regulatory influence of cortical mood-regulating regions over limbic regions.

  7. Response to antidepressants in major depressive disorder with melancholic features: the CRESCEND study.

    PubMed

    Yang, Su-Jin; Stewart, Robert; Kang, Hee-Ju; Kim, Seon-Young; Bae, Kyung-Yeol; Kim, Jae-Min; Jung, Sung-Won; Lee, Min-Soo; Yim, Hyeon-Woo; Jun, Tae-Youn

    2013-01-10

    This study aimed to determine whether major depressive disorders with melancholic and without melancholic features differ with respect to their responses to treatment with antidepressants. From a nationwide sample of 18 hospitals in South Korea, 559 presenting patients with major depressive disorder were recruited. The DSM-IV based Structured Clinical Interview was administered for confirmatory diagnoses and depression subtypes with/without melancholic features. After baseline evaluation, they received naturalistic clinician-determined antidepressant interventions. Assessment scales for evaluating depression (HAMD), anxiety (HAMA), global severity (CGI-s), and functioning (SOFAS) were administered at baseline and re-evaluated at 1, 2, 4, 8, and 12 weeks later. At baseline, the 243 (43.5%) participants with melancholic features were more likely to have a previous history of depression, and had higher HAMA and lower SOFAS scores. After adjustment for baseline status, participants with melancholic features were more likely to achieve and to experience shorter times to CGI-s remission and associated with an enhanced global symptomatic remission with any antidepressant treatment. They were more likely to achieve and to experience shorter times to CGI-s remission and this difference was strongest in those receiving selective serotonin reuptake inhibitor (SSRI) antidepressants treatment. The study was observational, and the treatment modality was naturalistic. These findings suggest a faster and more evident global response to pharmacotherapy in melancholia compared to other depressive syndromes, particularly where SSRI agents are used. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Association between antidepressant prescribing and suicide rates in OECD countries: an ecological study.

    PubMed

    Kamat, M A; Edgar, L; Niblock, P; McDowell, C; Kelly, C B

    2014-01-01

    We have conducted an ecological study to assess the association between antidepressant prescribing and suicide rates using the Organisation for Economic Co-operation and Development (OECD) health data, making this the largest ecological study in recent times. Data were derived for the years 1995-2008 from the OECD health data set. The residuals for all variables were adjusted for country and year within each country. These were then analysed to identify predictors of suicide rate. Pearson's rank correlation coefficient and linear regression model were employed to assess associations and identify significant predictors of suicide rate. Suicide rate has significant positive correlations with antidepressant rates (p=0.031) and unemployment (p=0.028). It also has a significant negative correlation with inpatient psychiatric beds (p=0.039). The actual coefficients are less than ±0.16, indicating weak relationships. After adjusting for other variables, the only variable that is a statistically significant predictor of suicide rate is antidepressant prescribing (p=0.005, r²=0.09). Our analysis using this large data set suggests a statistically significant, albeit weak positive, association between antidepressant prescribing and suicide rates. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Most Antidepressant Use in Primary Care Is Justified; Results of the Netherlands Study of Depression and Anxiety

    PubMed Central

    Piek, Ellen; van der Meer, Klaas; Hoogendijk, Witte J. G.; Penninx, Brenda W. J. H.; Nolen, Willem A.

    2011-01-01

    Background Depression is a common illness, often treated in primary care. Many studies have reported undertreatment with antidepressants in primary care. Recently, some studies also reported overtreatment with antidepressants. The present study was designed to assess whether treatment with antidepressants in primary care is in accordance with current guidelines, with a special focus on overtreatment. Methodology We used baseline data of primary care respondents from the Netherlands Study of Depression and Anxiety (NESDA) (n = 1610). Seventy-nine patients with treatment in secondary care were excluded. We assessed justification for treatment with antidepressant according to the Dutch primary care guidelines for depression and for anxiety disorders. Use of antidepressants was based on drug-container inspection or, if unavailable, on self-report. Results were recalculated to the original population of primary care patients from which the participants in NESDA were selected (n = 10,677). Principal Findings Of 1531 included primary care patients, 199 (13%) used an antidepressant, of whom 188 (94.5%) (possibly) justified. After recalculating these numbers to the original population (n = 10,677), we found 908 (95% CI 823 to 994) antidepressant users. Forty-nine (95% CI 20 to 78) of them (5.4%) had no current justification for an antidepressant, but 27 of them (54.5%) had a justified reason for an antidepressant at some earlier point in their life. Conclusions We found that overtreatment with antidepressants in primary care is not a frequent problem. Too long continuation of treatment seems to explain the largest proportion of overtreatment as opposed to inappropriate initiation of treatment. PMID:21479264

  10. Atypical Antidepressants

    MedlinePlus

    ... dangerous reactions when combined with certain medications or herbal supplements. Serotonin syndrome. Rarely, an antidepressant can cause high ... antidepressants, certain pain or headache medications, and the herbal supplement St. John's wort. Symptoms of serotonin syndrome include ...

  11. Anti-depressant medication use and C-reactive protein: results from two population-based studies.

    PubMed

    Hamer, Mark; Batty, G D; Marmot, Michael G; Singh-Manoux, Archana; Kivimäki, Mika

    2011-01-01

    The use of anti-depressant medication has been linked to cardiovascular disease (CVD). We examined the association between anti-depressant medication use and a marker of low grade systemic inflammation as a potential pathway linking anti-depressant use and CVD in two population based studies. Data were collected in a representative sample of 8131 community dwelling adults (aged 47.4±15.9 years, 46.7% male) from the Scottish Health Surveys (SHS). The use of anti-depressant medication was coded according to the British National Formulary and blood was drawn for the measurement of C-reactive protein (CRP). In a second study, we attempted to replicate our findings using longitudinal data from the Whitehall II study (n=4584, aged 55.5±5.9 years, mean follow-up 5.5 years). Antidepressants were used in 5.6% of the SHS sample, with selective serotonin reuptake inhibitors (SSRIs) being the most common. There was a higher risk of elevated CRP (>3 mg/L) in users of tricyclic antidepressant (TCA) medication (multivariate adjusted odds ratio (OR)=1.52, 95% CI, 1.07-2.15), but not in SSRI users (multivariate adjusted OR=1.07, 95% CI, 0.81-1.42). A longitudinal association between any antidepressant use and subsequent CRP was confirmed in the Whitehall cohort. In summary, the use of anti-depressants was associated with elevated levels of systemic inflammation independently from the symptoms of mental illness and cardiovascular co-morbidity. This might be a potential mechanism through which antidepressant medication increases CVD risk. Further data are required to explore the effects of dosage and duration of antidepressant treatment.

  12. Anti-depressant medication use and C-reactive protein: Results from two population-based studies

    PubMed Central

    Hamer, Mark; Batty, G. David; Marmot, Michael G.; Singh-Manoux, Archana; Kivimäki, Mika

    2010-01-01

    The use of anti-depressant medication has been linked to cardiovascular disease (CVD). We examined the association between anti-depressant medication use and a marker of low grade systemic inflammation as a potential pathway linking anti-depressant use and CVD in two population based studies. Data were collected in a representative sample of 8,131 community dwelling adults (aged 47.4 ± 15.9 yrs, 46.7% male) from the Scottish Health Surveys (SHS). The use of anti-depressant medication was coded according to the British National Formulary and blood was drawn for the measurement of C-reactive protein (CRP). In a second study, we attempted to replicate our findings using longitudinal data from the Whitehall II study (n=4584, aged 55.5 ± 5.9 yrs, mean follow-up 5.5 years). Antidepressants were used in 5.6% of the SHS sample, with selective serotonin reuptake inhibitors (SSRIs) being the most common. There was a higher risk of elevated CRP (>3 mg/L) in users of tricyclic antidepressant (TCA) medication (multivariate adjusted odds ratio (OR) = 1.52, 95% CI, 1.07 – 2.15), but not in SSRI users (multivariate adjusted OR = 1.07, 95% CI, 0.81 – 1.42). A longitudinal association between any antidepressant use and subsequent CRP was confirmed in the Whitehall cohort. In summary, the use of anti-depressants was associated with elevated levels of systemic inflammation independently from the symptoms of mental illness and cardiovascular co-morbidity. This might be a potential mechanism through which antidepressant medication increases CVD risk. Further data are required to explore the effects of dosage and duration of antidepressant treatment. PMID:20863880

  13. Influence of antidepressant drugs on chlorpromazine metabolism in human liver--an in vitro study.

    PubMed

    Wójcikowski, Jacek; Daniel, Władysława A

    2010-01-01

    The aim of the present study was to investigate the possible effects of antidepressant drugs (fluvoxamine, imipramine) on the metabolism of the aliphatic-type phenothiazine neuroleptic chlorpromazine in the human liver. The experiment was performed in vitro using human liver microsomes. The kinetic analysis of chlorpromazine metabolism carried out in the absence or presence of antidepressants showed that fluvoxamine potently inhibited chlorpromazine 5-sulfoxidation (K(i) = 2.8 μM), mono-N-demethylation (K(i) = 1.4 μM) and di-N-demethylation (K(i) = 1.1 μM) via a competitive mechanism at therapeutic antidepressant concentrations. Imipramine moderately diminished the rate of chlorpromazine 5-sulfoxidation (K(i) = 8.7 μM, competitive inhibition), mono-N-demethylation (K(i) = 16.0 μM, non-competitive inhibition) and di-N-demethylation (K(i) = 13.5 μM mixed inhibition). Considering the serious side-effects of chlorpromazine and some of its metabolites, metabolic interactions between this neuroleptic and antidepressant drugs (especially the chlorpromazine-fluvoxamine interaction) may be of pharmacological and clinical importance.

  14. Antidepressant Withdrawal

    MedlinePlus

    Diseases and Conditions Depression (major depressive disorder) If you stop taking antidepressants, could you experience antidepressant withdrawal? Do withdrawal symptoms mean you were addicted to the drug? Answers from Daniel K. Hall-Flavin, M.D. Antidepressant withdrawal is possible if you ...

  15. Liver Function Test Abnormalities in Depressed Patients Treated with Antidepressants: A Real-World Systematic Observational Study in Psychiatric Settings

    PubMed Central

    Verstuyft, Céline; Corruble, Emmanuelle; Perlemuter, Gabriel; Colle, Romain

    2016-01-01

    Background Concerning the risk of antidepressant induced liver injury, it is not clear whether psychiatrists perform a liver function test (LFT) and whether an increase in aminotransferase levels should contraindicate antidepressant treatment. Aim To evaluate LFT availability, the prevalence of LFT abnormalities and the probable cause of an altered LFT in patients with a major depressive episode (MDE) requiring an antidepressant drug. Methods We studied LFT evaluation in a real world psychiatric setting, in a sample of 321 consecutive patients with a current major depressive episode (MDE) requiring an antidepressant drug treatment, but without current alcohol or drug dependence or unstable medical disease. Results An LFT is performed in 36.1% (116/321) of depressed patients. One fifth of antidepressant-treated patients who had an LFT evaluation had abnormal results. The most frequent causes of LFT abnormalities were: NAFLD (nonalcoholic fatty liver disease) (7/321; 2.1%), acute alcohol consumption (4/321; 1.2%), antidepressant-induced liver injury (3/321; 0.9%), hepatitis C virus infection (2/321; 0.6%) and heart failure (1/321; 0.3%). The cause of LFT abnormalities was unknown in 32% of patients (8/25) due to the absence of etiological investigations. Conclusion These results demonstrate that an LFT is infrequently performed by psychiatrists in depressed patients requiring an antidepressant drug. Baseline LFT assessment and observations during the first six months of antidepressant treatment may be useful for detection of patients with pre-existing liver disease such as NAFLD, and early identification of cases of antidepressant-induced liver injury. An increase in aminotransferase levels may be related to an underlying liver disease, but does not contraindicate antidepressant treatment. PMID:27171561

  16. Tricyclic Antidepressants and Tetracyclic Antidepressants

    MedlinePlus

    ... dangerous reactions when combined with certain medications or herbal supplements. Serotonin syndrome. Rarely, an antidepressant can cause high ... antidepressants, certain pain or headache medications, and the herbal supplement St. John's wort. Signs and symptoms of serotonin ...

  17. Increased risk of antidepressant use in childhood cancer survivors: a Danish population-based cohort study.

    PubMed

    Lund, Lasse Wegener; Winther, J F; Cederkvist, L; Andersen, K K; Dalton, S O; Appel, C W; Rechnitzer, C; Schmiegelow, K; Johansen, C

    2015-03-01

    Childhood cancer survivors are at risk of both somatic and mental late effects, but large population-based studies of depression are lacking. Risk of antidepressant use was evaluated in a population-based cohort of 5452 Danish children treated for cancer in 1975-2009 by linkage to the National Prescription Drug Database, which worldwide is the oldest nationwide registry of prescription medication. Hazard ratios (HRs) for antidepressant use were estimated in a Cox proportional hazards model stratified on sex, with population comparisons as referents. Overall, childhood cancer survivors were at increased risk of having antidepressants prescribed (HR, 1.4; 95% confidence interval (CI), 1.3-1.5). The excess absolute risk of antidepressant use was 2.5 per 1000 person-years (95% CI, 1.7-3.3), equivalent to an excess of 2.5 survivors for every 100 survivors followed for 10years. Increased HRs of 30-50% were seen for survivors of cancers of all main groups (haematological malignancies, central nervous system (CNS) and solid tumors); the highest risk was among children treated with haematopoietic stem cell transplantation (HR, 1.9; 95% CI, 1.2-3.1). Our data suggested that the risk was most pronounced for children treated in the most recent calendar periods (test for interaction between cancer and calendar periods: P<0.001), especially for survivors of haematological cancers (P=0.007). Interaction analysis of the effect of parental socioeconomic position and psychiatric disease on the association between childhood cancer and antidepressant use indicated no modifying effect. Childhood cancer survivors should be followed-up for depression. Our results indicate an increasing need for follow-up especially in survivors treated by more recent, intensive anticancer treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. In vivo studies of effects of antidepressants on parotid salivary secretion in the rat.

    PubMed

    Johnsson, Martin; Winder, Michael; Zawia, Hana; Lödöen, Ida; Tobin, Gunnar; Götrick, Bengt

    2016-07-01

    Tricyclic antidepressants (TCA) are well-known xerogenic drugs, while antidepressants such as selective serotonin reuptake inhibitors (SSRI) are considered less xerogenic. The antimuscarinic effect of the TCAs has been considered to be the principal mechanism causing a dry mouth. Although the muscarinic receptor is commonly targeted by xerogenic pharmaceuticals, the salivation reflex arc may be affected at other levels as well. We currently wondered whether or not antidepressants exert an inhibition of the salivary reflex not only at the glandular level but at a central level as well. In this study, the effects of a TCA (clomipramine), a SSRI (citalopram) and a serotonin-noradrenaline reuptake inhibitor (SNRI; venlafaxine) were examined on reflex- (0.5M citric acid applied on the tongue) and methacholine-evoked salivary secretion. While all three compounds inhibited citric acid-evoked secretion (-40 to -60% at 5mg/kg i.v. of the antidepressants), only clomipramine inhibited methacholine-evoked secretion (-30% at 5mg/kg i.v.). On the contrary, both citalopram and venlafaxine increased the methacholine-evoked secretion (+44 to 49%). This was particularly obvious for the salivary protein output (>200%). In the presence of α- and β-adrenoceptor antagonists, the citalopram- and venlafaxine-induced increases were reduced. Thus, antidepressants irrespective of type may exert xerogenic effects by inhibiting the salivary reflex in the central nervous system. However, while TCAs may also hamper the secretory response by antimuscarinic effects, the SSRI and the SNRI groups of pharmaceuticals seem to lack this additional xerogenic mechanism indicating a better therapeutic profile and better opportunities for pharmacological treatment of drug-induced xerostomia. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Effect of antidepressant treatment on cognitive impairments associated with depression: a randomised longitudinal study.

    PubMed

    Shilyansky, Carrie; Williams, Leanne M; Gyurak, Anett; Harris, Anthony; Usherwood, Timothy; Etkin, Amit

    2016-05-01

    Antidepressant treatment failure is a common problem worldwide. In this study, we assess whether or not an important aspect of depression, cognitive impairment, is untreated by antidepressants by studying the effect of acute antidepressant treatment on a range of cognitive domains. In this randomised longitudinal study, which is part of the International Study to Predict Optimized Treatment in Depression (iSPOT-D) trial, we assessed the effects of acute antidepressant treatment in a large patient population, across clinical remission outcomes, on a range of cognitive domains: attention, response inhibition, executive function during visuospatial navigation, cognitive flexibility, verbal memory, working memory, decision speed, information processing speed, and psychomotor response speed. We enrolled patients from primary or specialty care clinics in a multicentre, international, open-label, randomised, prospective trial. Eligible patients (aged 18-65 years) were previously untreated or were willing to undergo a 1-week medication washout before the study start, and could not have had inadequate response to study medications in the past. We enrolled a large population of medication-free (ie, untreated) outpatients in a depressive episode and assessed them for cognitive function at enrolment (pre-treatment), and again after 8 weeks of treatment with one of three antidepressant drugs (escitalopram, sertraline, or venlafaxine extended-release). Patients were randomly assigned (1:1:1) to one of the three antidepressants using a blocked randomisation procedure (block size of 12). As a comparison group, we also simultaneously enrolled matched healthy participants. Healthy participants received no medication or intervention, but were assessed for change in cognitive and clinical measures during the same interval and testing protocol. Therefore, this group acts as a test-retest control for the primary outcome measure examined in this study, change in cognitive measures over 8

  20. Use of a 12 months' self-referral reminder to facilitate uptake of bowel scope (flexible sigmoidoscopy) screening in previous non-responders: a London-based feasibility study.

    PubMed

    Kerrison, Robert S; McGregor, Lesley M; Marshall, Sarah; Isitt, John; Counsell, Nicholas; Wardle, Jane; von Wagner, Christian

    2016-03-29

    In March 2013, NHS England extended its national Bowel Cancer Screening Programme to include 'one-off' Flexible Sigmoidoscopy screening (NHS Bowel Scope Screening, BSS) for men and women aged 55. With less than one in two people currently taking up the screening test offer, there is a strong public health mandate to develop system-friendly interventions to increase uptake while the programme is rolling out. This study aimed to assess the feasibility of sending a reminder to previous BSS non-responders, 12 months after the initial invitation, with consideration for its potential impact on uptake. This study was conducted in the ethnically diverse London Boroughs of Brent and Harrow, where uptake is below the national average. Between September and November 2014, 160 previous non-responders were randomly selected to receive a reminder of the opportunity to self-refer 12 months after their initial invitation. The reminder included instructions on how to book an appointment, and provided options for the time and day of the appointment and the gender of the endoscopist performing the test. To address barriers to screening, the reminder was sent with a brief locally tailored information leaflet designed specifically for this study. Participants not responding within 4 weeks were sent a follow-up reminder, after which there was no further intervention. Self-referral rates were measured 8 weeks after the delivery of the follow-up reminder and accepted as final. Of the 155 participants who received the 12 months' reminder (returned to sender, n=5), 30 (19.4%) self-referred for an appointment, of which 24 (15.5%) attended and were successfully screened. Attendance rates differed by gender, with significantly more women attending an appointment than men (20.7% vs 8.8%, respectively; OR=2.73, 95% CI=1.02-7.35, P=0.05), but not by area (Brent vs Harrow) or area-level deprivation. Of the 30 people who self-referred for an appointment, 27 (90%) indicated a preference for a same

  1. Relative efficacy and tolerability of vortioxetine versus selected antidepressants by indirect comparisons of similar clinical studies.

    PubMed

    Llorca, Pierre-Michel; Lançon, Christophe; Brignone, Mélanie; Rive, Benoît; Salah, Samir; Ereshefsky, Larry; Francois, Clément

    2014-12-01

    Vortioxetine is an antidepressant with multimodal activity which has shown efficacy in major depressive disorder (MDD) patients in six of ten short-term, randomized, placebo-controlled trials (completed end 2012). We performed meta-regression analyses to indirectly compare vortioxetine to seven marketed antidepressants with different mechanisms of action. To ensure study comparability, only experimental drug and placebo arms from placebo-controlled registration studies were included in primary analyses. The main outcomes were efficacy (standardized mean difference in change from baseline to 2 months on primary endpoint [MADRS/HAM-D]), and tolerability (withdrawal rate due to adverse events). For efficacy, estimates of treatment effect (negative estimates favor vortioxetine) for vortioxetine versus comparators were: agomelatine, -0.16 (p = 0.11); desvenlafaxine, 0.03 (p = 0.80); duloxetine, 0.09 (p = 0.42); escitalopram, -0.05 (p = 0.70); sertraline, -0.04 (p = 0.83); venlafaxine IR/XR, 0.12 (p = 0.33); and vilazodone, -0.25 (p = 0.11). For tolerability, all but one combination was numerically in favor of vortioxetine (odds ratio < 1), although not all differences were statistically significant: agomelatine, 1.77 (p = 0.03); desvenlafaxine, 0.58 (p = 0.04); duloxetine, 0.75 (p = 0.26); escitalopram, 0.67 (p = 0.28); sertraline, 0.30 (p = 0.01); venlafaxine, 0.47 (p = 0.01); and vilazodone, 0.64 (p = 0.18). Sensitivity analyses did not significantly alter antidepressant effect estimates or relative ranking. These meta-regression data show that vortioxetine offers a comparable or favorable combination of efficacy (measured by MADRS/HAM-D) and tolerability (measured by withdrawal rate due to adverse events) versus other antidepressants in registration studies in MDD. Alternative methods like mixed-treatment comparison and inclusion of all randomized studies and active reference arms may provide complementary information to this analysis (more evidence but also more

  2. Cost-effectiveness of early responders versus early nonresponders to atypical antipsychotic therapy

    PubMed Central

    Peng, Xiaomei; Ascher-Svanum, Haya; Faries, Douglas E; Stauffer, Virginia L; Kollack-Walker, Sara; Kinon, Bruce J; Kane, John M

    2011-01-01

    Background: To compare the cost-effectiveness of treating early responders versus early nonresponders to an atypical antipsychotic (risperidone) and the cost-effectiveness of treating early nonresponders maintained on risperidone versus those switched to olanzapine. Methods: This post hoc analysis used data from a randomized, double-blind, 12-week schizophrenia study (Study Code: HGMN, n = 628). Participants were initially assigned to risperidone therapy. Early response was defined as a ≥ 20% improvement on the Positive and Negative Syndrome Scale (PANSS) total score from baseline to two weeks. Early responders continued on risperidone, whereas early nonresponders were randomized in a double-blind manner to continue on risperidone or switch to olanzapine for 10 additional weeks. Early responders and early nonresponders maintained on risperidone were compared for health-state utilities (benefits) and total cost over the 12-week study; early nonresponders maintained on risperidone or switched to olanzapine were compared from randomization (10-week period). Utilities were derived from the PANSS and adverse events. Mixed models were used to assess group differences in utilities. Treatment costs were calculated based on health states. Incremental cost-effectiveness ratios were then utilized to compare treatment groups. Results: Early responders to risperidone had significantly greater total utility and lower total treatment costs than early nonresponders to risperidone. Compared with early nonresponders who continued on risperidone, those who were switched to olanzapine had significantly higher total utility scores at endpoint and numerically lower total treatment costs, reflecting significantly lower nonmedication treatment costs, even though medication costs were significantly higher compared with generic risperidone. Conclusion: Treatment of early responders was more cost-effective than treatment of early nonresponders to atypical antipsychotic therapy. Switching

  3. Responder and nonresponder patients exhibit different peripheral transcriptional signatures during major depressive episode

    PubMed Central

    Belzeaux, R; Bergon, A; Jeanjean, V; Loriod, B; Formisano-Tréziny, C; Verrier, L; Loundou, A; Baumstarck-Barrau, K; Boyer, L; Gall, V; Gabert, J; Nguyen, C; Azorin, J-M; Naudin, J; Ibrahim, E C

    2012-01-01

    To date, it remains impossible to guarantee that short-term treatment given to a patient suffering from a major depressive episode (MDE) will improve long-term efficacy. Objective biological measurements and biomarkers that could help in predicting the clinical evolution of MDE are still warranted. To better understand the reason nearly half of MDE patients respond poorly to current antidepressive treatments, we examined the gene expression profile of peripheral blood samples collected from 16 severe MDE patients and 13 matched controls. Using a naturalistic and longitudinal design, we ascertained mRNA and microRNA (miRNA) expression at baseline, 2 and 8 weeks later. On a genome-wide scale, we detected transcripts with roles in various biological processes as significantly dysregulated between MDE patients and controls, notably those involved in nucleotide binding and chromatin assembly. We also established putative interactions between dysregulated mRNAs and miRNAs that may contribute to MDE physiopathology. We selected a set of mRNA candidates for quantitative reverse transcriptase PCR (RT-qPCR) to validate that the transcriptional signatures observed in responders is different from nonresponders. Furthermore, we identified a combination of four mRNAs (PPT1, TNF, IL1B and HIST1H1E) that could be predictive of treatment response. Altogether, these results highlight the importance of studies investigating the tight relationship between peripheral transcriptional changes and the dynamic clinical progression of MDE patients to provide biomarkers of MDE evolution and prognosis. PMID:23149449

  4. EEG connectivity between the subgenual anterior cingulate and prefrontal cortices in response to antidepressant medication.

    PubMed

    Iseger, Tabitha A; Korgaonkar, Mayuresh S; Kenemans, J Leon; Grieve, Stuart M; Baeken, Chris; Fitzgerald, Paul B; Arns, Martijn

    2017-02-22

    Antidepressant medication is the most common treatment for major depressive disorder (MDD), however, the precise working mechanism underlying these treatments remains unclear. Recent neuromodulation treatments demonstrate that direct stimulation of the dorsolateral prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC), and subgenual anterior cingulate (sgACC) relate to clinical improvement, suggesting connectivity alterations of the DLPFC-DMPFC-sgACC network to mediate antidepressant response. The international Study to Predict Optimized Treatment in Depression (iSPOT-D) is an international multicentre study that collected EEG data for 1008 MDD patients, randomized to 3 different antidepressant medications (N=447 MDD with complete pre- and post-treatment data and N=336 non-MDD). Treatment response was defined by a decline of >50% on the Hamilton Rating Score for Depression (HRSD17). We investigated whether connectivity in alpha and theta frequencies of the DLPFC-DMPFC-sgACC network changed from pre- to post-treatment between: (i) patients and controls, and (ii) responders (R) and non-responders (NR). Women exhibited higher alpha and theta connectivity compared to males, both pre- and post-treatment. Furthermore, theta, but not alpha, hypo-connectivity was found for MDD patients. A decreased alpha connectivity after treatment was found only for male responders, while non-responders and females exhibited no changes in alpha connectivity. Decreasing alpha connectivity could potentially serve as a treatment emergent biomarker, in males only. Furthermore, it could be useful to a priori stratify by gender for future MDD studies.

  5. Divorce and subsequent increase in uptake of antidepressant medication: a Finnish registry-based study on couple versus individual effects.

    PubMed

    Monden, Christiaan W S; Metsä-Simola, Niina; Saarioja, Saska; Martikainen, Pekka

    2015-02-19

    There is an average negative mental health effect for individuals who experience divorce. Little is known whether the pattern of such divorce effects varies within couples. We study whether the husband and wife experience similar harmful effects of divorce, whether they experience opposite effects, or whether divorce effects are purely individual. We use Finnish registry data to compare changes over a period of 5 years in antidepressant use of husbands and wives from 4,558 divorcing couples to 108,637 continuously married pairs aged 40-64, all of whom were healthy at baseline. In the period three years before and after divorce antidepressant use increases substantially. However, the likelihood of uptake of antidepressant medication during this process of divorce by one partner appears to be independent of medication uptake in the other partner. In contrast, among continuously married couples there is a clear pattern of convergence: If one partner starts to use antidepressants this increases the likelihood of uptake of antidepressant medication in the other partner. Our findings suggest that divorce effects on antidepressant use are individual and show no pattern of either convergence or divergence at the level of the couple. The increased incidence of antidepressant use associated with divorce occurs in individuals independent of what happens to their ex-partner.

  6. Antidepressant Drugs and the Risk of Intracranial Bleeding: Parsing an Observational Study.

    PubMed

    Howland, Robert H

    2016-02-01

    Observational studies have suggested that antidepressant drug use is associated with a small but increased risk of intracranial bleeding. Because of the widespread use of antidepressant drugs and the potential public health significance of this finding, the current article critically evaluates the methodology and findings of a recently published observational study. Observational studies reveal associations, but cannot establish causality. Establishing causality from observed associations requires evidence from different scientific perspectives. Claims arising from observational studies are likely to be wrong, especially for small effects, because of bias and confounding. Statistical testing does not prove the validity of an association, nor does a meta-analysis of multiple observational studies. A valid association may not be clinically meaningful if the magnitude of the effect is small or the outcome is rare. Based on a critical analysis of these observational studies, it is concluded that the risk of intracranial bleeding associated with antidepressant drugs is likely to be a false alarm. [Journal of Psychosocial Nursing and Mental Health Services, 54(2), 21-24.].

  7. Antidepressive and anxiolytic effects of ayahuasca: a systematic literature review of animal and human studies.

    PubMed

    Dos Santos, Rafael G; Osório, Flávia L; Crippa, José Alexandre S; Hallak, Jaime E C

    2016-03-01

    To conduct a systematic literature review of animal and human studies reporting anxiolytic or antidepressive effects of ayahuasca or some of its isolated alkaloids (dimethyltryptamine, harmine, tetrahydroharmine, and harmaline). Papers published until 3 April 2015 were retrieved from the PubMed, LILACS and SciELO databases following a comprehensive search strategy and using a predetermined set of criteria for article selection. Five hundred and fourteen studies were identified, of which 21 met the established criteria. Studies in animals have shown anxiolytic and antidepressive effects of ayahuasca, harmine, and harmaline, and experimental studies in humans and mental health assessments of experienced ayahuasca consumers also suggest that ayahuasca is associated with reductions in anxiety and depressive symptoms. A pilot study reported rapid antidepressive effects of a single ayahuasca dose in six patients with recurrent depression. Considering the need for new drugs that produce fewer adverse effects and are more effective in reducing anxiety and depression symptomatology, the described effects of ayahuasca and its alkaloids should be further investigated.

  8. Age-Related Response to Redeemed Antidepressants Measured by Completed Suicide in Older Adults: A Nationwide Cohort Study

    PubMed Central

    Erlangsen, Annette; Conwell, Yeates

    2013-01-01

    Objective To examine if the suicide rate of older adults prescribed antidepressants varies with age and to assess the proportion of older adults who died by suicide that had recently been prescribed antidepressants. Methods A population-based cohort study using a nationwide linkage of individual-level records was conducted on all persons aged 50+ living in Denmark during 1996–2006 (1,215,524 men and 1,343,568 women). Suicide rates by treatment status were calculated using data on all antidepressant prescriptions redeemed at pharmacies. Results Individual-level data covered 9,354,620 and 10,720,639 person-years for men and women, respectively. Men aged 50–59 who received antidepressants had a mean suicide rate of 185 (95% confidence interval [CI]: 160–211) per 100,000, whereas for those aged 80+ the rate was 119 (95% CI: 91–146). For women, the corresponding values were 82 (95% CI: 70–94) and 28 (95% CI: 20–35). Logistic regression showed a 2% and 3% decline in the rate for men and women, respectively, considered in treatment with antidepressants, with each additional year of age. An opposite trend was found for persons not in treatment. Fewer persons aged 80+ dying by suicide had received antidepressant prescriptions during the last months of life than younger persons. Conclusion An age-dependent decline in suicide rate for antidepressant recipients was identified. One reason could be that older adults respond better to antidepressants than younger age groups. Still, the increasing gap with age between estimated prevalence of depression and antidepressant prescription rate in persons dying by suicide underscores the need for assessment of depression in the oldest old. PMID:23567434

  9. [Antidepressants, depression and suicide].

    PubMed

    Rihmer, Zoltán

    2013-09-01

    The goal of this paper is to analyse the complex relationship between antidepressants, depression and suicide. Review and synthesis of the Hungarian and English language international literature, published on this topic in the last 15 years. Large-scale, retrospective and prospective, naturalistic ("real life") studies show that compared to patients without treatment antidepressants and mood stabilizers reduce the risk of completed and attempted suicide by about 80%. This anti-suicidal potential is significantly higher than the small increase in suicidality of patients taking antidepressants in placebo controlled randomized Phase II/III trials. New data show that based on clinical data this small subgroup can be identified and successfully treated using specific therapy. Suicidal behaviour in patients taking antidepressants is mostly the consequence of the lack of antidepressant effect and is rarely the result of suicide-inducing potential of antidepressants. This rare latter case is most frequently the consequence of antidepressant monotherapy of bipolar depression. Appropriate use of antidepressants and mood stabilizers plays a key role in suicide prevention of patients with affective disorders.

  10. Comparative study of cognitive impairment between medicated and medication-free patients with remitted major depression: class-specific influence by tricyclic antidepressants and newer antidepressants.

    PubMed

    Nagane, Akiko; Baba, Hajime; Nakano, Yoshiyuki; Maeshima, Hitoshi; Hukatsu, Mana; Ozawa, Kazuhiro; Suzuki, Toshihito; Arai, Heii

    2014-08-15

    Patients with major depressive disorder (MDD) are known to present with cognitive deficits; however, the presence of these deficits in the remitted state have been inconsistent. One of the most important factors potentially contributing to inconsistencies between studies may be the influence of medications. To explore the influence of antidepressants on cognitive performance in remitted MDD, we evaluated memory and executive functions using Wechsler Memory Scale-Revised and Stroop Color and Word Test, and compared performance among 50 medicated (29 treated with tricyclic antidepressants [TCA], 21 treated with selective serotonin reuptake inhibitors or serotonin noradrenalin reuptake inhibitors) and 19 medication-free MDD patients and 31 controls. The results showed that all 3 MDD groups had significantly lower performance for verbal memory compared with controls. Both medicated groups showed significantly lower performance for visual memory compared with controls; however, the medication-free group did not differ from controls. For the executive function, only the TCA group showed a significantly lower performance compared with controls. These results suggest that cognitive impairment remained even in remitted patients with MDD, however, part of this impairment may be influenced by class-specific antidepressant side effects. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. Off-label indications for antidepressants in primary care: descriptive study of prescriptions from an indication based electronic prescribing system

    PubMed Central

    Motulsky, Aude; Abrahamowicz, Michal; Eguale, Tewodros; Buckeridge, David L; Tamblyn, Robyn

    2017-01-01

    Objective To examine off-label indications for antidepressants in primary care and determine the level of scientific support for off-label prescribing. Design Descriptive study of antidepressant prescriptions written by primary care physicians using an indication based electronic prescribing system. Setting Primary care practices in and around two major urban centres in Quebec, Canada. Participants Patients aged 18 years or older who visited a study physician between 1 January 2003 and 30 September 2015 and were prescribed an antidepressant through the electronic prescribing system. Main outcome measures Prevalence of off-label indications for antidepressant prescriptions by class and by individual drug. Among off-label antidepressant prescriptions, the proportion of prescriptions in each of the following categories was measured: strong evidence supporting use of the prescribed drug for the respective indication; no strong evidence for the prescribed drug but strong evidence supporting use of another drug in the same class for the indication; or no strong evidence supporting use of the prescribed drug and all other drugs in the same class for the indication. Results 106 850 antidepressant prescriptions were written by 174 physicians for 20 920 adults. By class, tricyclic antidepressants had the highest prevalence of off-label indications (81.4%, 95% confidence interval, 77.3% to 85.5%), largely due to a high off-label prescribing rate for amitriptyline (93%, 89.6% to 95.7%). Trazodone use for insomnia was the most common off-label use for antidepressants, accounting for 26.2% (21.9% to 30.4%) of all off-label prescriptions. For only 15.9% (13.0% to 19.3%) of all off-label prescriptions, the prescribed drug had strong scientific evidence for the respective indication. For 39.6% (35.7% to 43.2%) of off-label prescriptions, the prescribed drug did not have strong evidence but another antidepressant in the same class had strong evidence for the respective

  12. A genome-wide association study of antidepressant response in Koreans.

    PubMed

    Myung, W; Kim, J; Lim, S-W; Shim, S; Won, H-H; Kim, Seonwoo; Kim, Sangha; Lee, M-S; Chang, H S; Kim, J-W; Carroll, B J; Kim, D K

    2015-09-08

    We conducted a three-stage genome-wide association study (GWAS) of response to antidepressant drugs in an ethnically homogeneous sample of Korean patients in untreated episodes of nonpsychotic unipolar depression, mostly of mature onset. Strict quality control was maintained in case selection, diagnosis, verification of adherence and outcome assessments. Analyzed cases completed 6 weeks of treatment with adequate plasma drug concentrations. The overall successful completion rate was 85.5%. Four candidate single-nucleotide polymorphisms (SNPs) on three chromosomes were identified by genome-wide search in the discovery sample of 481 patients who received one of four allowed selective serotonin reuptake inhibitor (SSRI) antidepressant drugs (Stage 1). In a focused replication study of 230 SSRI-treated patients, two of these four SNP candidates were confirmed (Stage 2). Analysis of the Stage 1 and Stage 2 samples combined (n = 711) revealed GWAS significance (P = 1.60 × 10(-8)) for these two SNP candidates, which were in perfect linkage disequilibrium. These two significant SNPs were confirmed also in a focused cross-replication study of 159 patients treated with the non-SSRI antidepressant drug mirtazapine (Stage 3). Analysis of the Stage 1, Stage 2 and Stage 3 samples combined (n = 870) also revealed GWAS significance for these two SNPs, which was sustained after controlling for gender, age, number of previous episodes, age at onset and baseline severity (P = 3.57 × 10(-8)). For each SNP, the response rate decreased (odds ratio=0.31, 95% confidence interval: 0.20-0.47) as a function of the number of minor alleles (non-response alleles). The two SNPs significantly associated with antidepressant response are rs7785360 and rs12698828 of the AUTS2 gene, located on chromosome 7 in 7q11.22. This gene has multiple known linkages to human psychological functions and neurobehavioral disorders. Rigorous replication efforts in other ethnic populations are recommended.

  13. CNS effects of citalopram, a new serotonin inhibitor antidepressant (a quantitative pharmaco-electroencephalography study).

    PubMed

    Itil, T M; Menon, G N; Bozak, M M; Itil, K Z

    1984-01-01

    Citalopram, a new phthalane derivative and a specific serotonin re-uptake inhibitor in animal pharmacological tests, was evaluated in a double-blind, crossover, quantitative pharmaco-EEG (QPEEGTM) study in healthy human volunteers. The CNS effects of citalopram are linear, dose- and time-related, can statistically be differentiated from placebo, and indicate a rapid onset of effects with short duration. According to the Computer Data Bank, citalopram has a mode of action similar to mood elevators (antidepressants) with fewer sedative properties. Thus the therapeutic action of citalopram is predicted to be similar to desipramine and protriptyline from the tricyclics, and fluvoxamine from non-tricyclics. According to data bank assessment, it is hypothesized that the single antidepressant dose of citalopram is to be more than 25 mg, which should be given t.i.d. in clinical trials.

  14. Research on antidepressants in India

    PubMed Central

    Avasthi, Ajit; Grover, Sandeep; Aggarwal, Munish

    2010-01-01

    Data suggests that antidepressants are useful in the management of depressive disorders, anxiety disorders, sexual dysfunction, eating disorders, impulse control disorders, enuresis, aggression and some personality disorders. Research focusing on the usefulness of antidepressants in India has more or less followed the trends seen in the West. Most of the studies conducted in India have evaluated various antidepressants in depression. In this article, we review studies conducted in India on various antidepressants. The data suggests that antidepressants have been evaluated mainly in the acute phase treatment and rare studies have evaluated the efficacy in continuation phase treatment. PMID:21836704

  15. Primary adherence to antidepressant prescriptions in primary health care: a population-based study in Sweden.

    PubMed

    Freccero, Carl; Sundquist, Kristina; Sundquist, Jan; Ji, Jianguang

    2016-01-01

    Medical adherence is important in the treatment of depression. Primary medical adherence, i.e. patients collecting their newly prescribed medications from pharmacies, is very different depending on the drug prescribed To assess the rate of primary medical adherence in patients prescribed antidepressants and to identify characteristics that make patients less likely to pick up prescriptions. An observational study was performed using primary health care data from Sweden on patients who were prescribed antidepressants. Univariate and multivariate logistic regression was used to determine differences in pick-up rate according to patient characteristics. Pick-up rate, defined as collection of a prescription within 30 days. A total of 11 624 patients received an antidepressant prescription during the study period, and the overall pick-up rate was 85.1%. The pick-up rate differed according to country of birth: individuals born in the Middle East and other countries outside Europe had lower primary medical adherence than Swedes, with adjusted odds ratios (ORs) of 0.58 and 0.67, respectively. Patients at ages 64-79 years had a higher pick-up rate compared with those aged 25-44 years (OR 1.71). Divorced patients had a lower rate compared with married patients (OR 0.80). Immigrants from the Middle East and other countries outside Europe and younger and divorced patients had lower primary medical adherence, which calls for clinical attention and preventive measures. KEY POINTS Primary medical adherence is important in the treatment of depression. Are patient characteristics associated with primary medical adherence? The overall primary medical adherence rate was 85%. The rate differed by country of birth, age at diagnosis of depression, and marital status. Clinical attention is needed in patients who do not pick up their antidepressants.

  16. [Experimental study of 3-oxypiridine and succinic acid derivates antidepressant activity in mice].

    PubMed

    Volchegorskiĭ, I A; Miroshnichenko, I Iu; Rassokhina, L M; Faĭzullin, R M

    2013-01-01

    Effect of Russian 3-oxypiridine and succinic acid derivatives (emoxipin, reamberin and mexidol) on duration of behavioral despair in mice in forced swimming test (by Porsolot) and tail suspension test (by Steru) was investigated. In addition impact assessment of studied medicinal products (MP) on animals' behavior in open field test was performed. Amitriptyline and alpha-lipoic acid were used as reference drugs. It was determined that single delivery of all studied drugs in optimal doses eqvivalent to therapeutic range for human reduces lasting of behavioral despair in Porsolot and Steru tests. This effect of reamberin, mexidol and alpha-lipoic acid indicates their antidepressant action unrelated to stimulatory activity, as far as these MPs like amitriptyline show sedative action in open field test. Reduction of behavioral despair due to effect of emoxipin in relative low doses was associated with increase of mice activity in open field test and so it can't be considered to be antidepressant action per se. Increase of emoxipin dose leads to progressive decrease of its stimulatory effect impact in behavioral despair reduction and induce antidepressant effect in the setting of sedation.

  17. The place of additional individual psychotherapy in the treatment of alcoholism: a randomized controlled study in nonresponders to anticraving medication-results of the PREDICT study.

    PubMed

    Berner, Michael M; Wahl, Sonja; Brueck, Rigo; Frick, Katrin; Smolka, Robert; Haug, Monika; Hoffmann, Sabine; Reinhard, Iris; Leménager, Tagrid; Gann, Horst; Batra, Anil; Mann, Karl

    2014-04-01

    Goal of the presented study is to evaluate whether alcohol-dependent patients given additional individual psychotherapy after a heavy relapse during pharmacotherapy remain abstinent for longer than those who continue with pharmacotherapy alone. In a randomized, multicenter study, 109 alcohol-dependent patients who had suffered a heavy relapse either while receiving anticraving medication or placebo were randomized into 2 groups. One group received medication, medical management, and additional individual, disorder-specific, cognitive-behavioral psychotherapy, while the control group received medication and medical management only. Main outcome was defined as days until first heavy relapse. Fifty-four patients were randomized to the psychotherapy group, 55 to the control group. Intention-to-treat and completer analyses found no differences between groups, whereas as-treated analyses (patients who actually received psychotherapy compared with those who did not) found a significant effect of psychotherapy. Our data indicate that patients that are willing to attend psychotherapy benefit from receiving psychotherapy in addition to pharmacotherapy. We suggest that it may be beneficial to consider patients' preferences concerning psychotherapy at an earlier stage during treatment. Copyright © 2013 by the Research Society on Alcoholism.

  18. A study on evalution of antidepressant effect of imipramine adjunct with Aswagandha and Bramhi.

    PubMed

    Maity, T; Adhikari, A; Bhattacharya, K; Biswas, S; Debnath, P K; Maharana, C S

    2011-12-01

    Depressive disorders increase the risks of self-harm or even suicide in patients. Indigenous drugs are being tried to treat such patient along with conventional antidepressant drugs. This study was planned to investigate the antidepressant action of Ashwagandha and Bramhi and also to confirm its efficacy in the behavioural despair animal model of depression. Normal saline as control (5 ml/kg), Imipramine as standard (16, 32, 64 mg/ kg) and Ashwagandha (50, 100, 150 mg/kg), Bramhi (20, 40, 80 mg/kg) as test drugs were introduced to the albino rats weighing between 200-250 gm for 2 weeks, 1 hr before electric shock in Learned helplessness test (LHT) and swimming in Forced swimming test (FST). Effects of individual drugs as well as their combination were evaluated. Avoidance response, escape failure and immobility period in case of Imipramine and Ashwagandha showed highly significant (p < 0.01) result on individual use. There was no significant result in case of Bramhi used alone except in escape failure and immobility period (FST), where at higher doses it showed significant (p < 0.01) result. But combination of Bramhi and Ashwagandha in low doses with low dose of Imipramine gave a highly significant result (p < 0.01) in all the parameters. Ashwagandha had significant antidepressant action, but Bramhi had not when used alone. Combination of these two indigenous drug with Imipramine showed high efficacy in animal model.

  19. Unrecognised bipolar disorder among UK primary care patients prescribed antidepressants: an observational study.

    PubMed

    Hughes, Tom; Cardno, Alastair; West, Robert; Marino-Francis, Federica; Featherstone, Imogen; Rolling, Keeley; Locker, Alice; McLintock, Kate; House, Allan

    2016-02-01

    Bipolar disorder is not uncommon, is associated with high disability and risk of suicide, often presents with depression, and can go unrecognised. To determine the prevalence of unrecognised bipolar disorder among those prescribed antidepressants for depressive or anxiety disorder in UK primary care; whether those with unrecognised bipolar disorder have more severe depression than those who do not; and the accuracy of a screening questionnaire for bipolar disorder, the Mood Disorder Questionnaire (MDQ), in this setting. Observational primary care study of patients on the lists of 21 general practices in West Yorkshire aged 16-40 years and prescribed antidepressant medication. Participants were recruited using primary care databases, interviewed using a diagnostic interview, and completed the screening questionnaire and rating scales of symptoms and quality of life. The prevalence of unrecognised bipolar disorder was 7.3%. Adjusting for differences between the sample and a national database gives a prevalence of 10.0%. Those with unrecognised bipolar disorder were younger and had greater lifetime depression. The predictive value of the MDQ was poor. Among people aged 16-40 years prescribed antidepressants in primary care for depression or anxiety, there is a substantial proportion with unrecognised bipolar disorder. When seeing patients with depression or anxiety disorder, particularly when they are young or not doing well, clinicians should review the life history for evidence of unrecognised bipolar disorder. Some clinicians might find the MDQ to be a useful supplement to non-standardised questioning. © British Journal of General Practice 2016.

  20. Unrecognised bipolar disorder among UK primary care patients prescribed antidepressants: an observational study

    PubMed Central

    Hughes, Tom; Cardno, Alastair; West, Robert; Marino-Francis, Federica; Featherstone, Imogen; Rolling, Keeley; Locker, Alice; McLintock, Kate; House, Allan

    2016-01-01

    Background Bipolar disorder is not uncommon, is associated with high disability and risk of suicide, often presents with depression, and can go unrecognised. Aim To determine the prevalence of unrecognised bipolar disorder among those prescribed antidepressants for depressive or anxiety disorder in UK primary care; whether those with unrecognised bipolar disorder have more severe depression than those who do not; and the accuracy of a screening questionnaire for bipolar disorder, the Mood Disorder Questionnaire (MDQ), in this setting. Design and setting Observational primary care study of patients on the lists of 21 general practices in West Yorkshire aged 16–40 years and prescribed antidepressant medication. Method Participants were recruited using primary care databases, interviewed using a diagnostic interview, and completed the screening questionnaire and rating scales of symptoms and quality of life. Results The prevalence of unrecognised bipolar disorder was 7.3%. Adjusting for differences between the sample and a national database gives a prevalence of 10.0%. Those with unrecognised bipolar disorder were younger and had greater lifetime depression. The predictive value of the MDQ was poor. Conclusion Among people aged 16–40 years prescribed antidepressants in primary care for depression or anxiety, there is a substantial proportion with unrecognised bipolar disorder. When seeing patients with depression or anxiety disorder, particularly when they are young or not doing well, clinicians should review the life history for evidence of unrecognised bipolar disorder. Some clinicians might find the MDQ to be a useful supplement to non-standardised questioning. PMID:26740604

  1. Use of Tetrabenazine in Huntington Disease Patients on Antidepressants or with Advanced Disease: Results from the TETRA-HD Study

    PubMed Central

    Dorsey, Ray; Biglan, Kevin; Eberly, Shirley; Auinger, Peggy; Brocht, Alicia; Umeh, Chizoba C.; Oakes, David; Clarence-Smith, Kathleen; Marshall, Frederick; Shoulson, Ira; Frank, Samuel

    2011-01-01

    The safety and effectiveness of tetrabenazine in different sub-populations of Huntington disease (HD) is not known. In this study, we evaluated the safety of tetrabenazine in individuals on an antidepressant and its effectiveness in advanced HD. Tetrabenazine was not associated with an increased incidence of depressed mood among those taking antidepressants and was effective at reducing chorea in those with advanced HD. PMID:22139861

  2. Use of antidepressants in Parkinson's disease: A Swedish register-based study of over 1.5 million older people.

    PubMed

    Haasum, Ylva; Fastbom, Johan; Johnell, Kristina

    2016-06-01

    It has been suggested that depression in Parkinson's Disease (PD) is often unrecognized and undertreated. However, few previous studies have studied the use of antidepressants in a large sample of both home-dwelling and institutionalized elderly persons with PD. We aimed to study the use of antidepressants in older persons using anti-parkinson drugs (APD, used as a proxy for PD), stratified by residential setting. We analyzed individual data on age, sex, residential setting and drug use in over 1.5 million older persons in the Swedish Prescribed Drug Register on 31th of December 2013. Twenty-two percent of the home-dwellers and 50% of the institutionalized elderly persons with APD used antidepressants. Persons with APD had a higher probability of use of any antidepressant compared to persons without APD. A selective serotonin reuptake inhibitor (SSRI) was the most commonly used antidepressants in both settings followed by mirtazapin. The high use of antidepressants among older persons with APD warrants further studies on the quality of treatment of depression in PD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Person-related work and incident use of antidepressants: relations and mediating factors from the Danish work environment cohort study.

    PubMed

    Madsen, Ida E H; Diderichsen, Finn; Burr, Hermann; Rugulies, Reiner

    2010-11-01

    Previous Danish studies have shown that employees who "work with people" (i.e., do person-related work) are at increased risk of hospitalization with a diagnosis of depression. However, these studies were purely register-based and consequently unable to point to factors underlying this elevated risk. This paper examines whether person-related work is associated with incident use of antidepressants, and whether this association is mediated by several work environment exposures. Self-reported data from the Danish work environment cohort study in 2000 were linked with the use of antidepressants between 2001-2006. We included 4958 respondents in our study after excluding those with severe depressive symptoms or use of antidepressants at baseline. Compared to employees doing non-person-related work, the use of antidepressants was increased statistically significantly for healthcare workers and statistically non-significantly for educational workers. The use of antidepressants was not elevated for social or customer service workers, or those doing "other" types of person-related work. The increased risks of antidepressant-use for healthcare and educational workers were attenuated when adjusted for emotional demands at work. The results imply that healthcare and educational workers in Denmark are at increased risk of depression and that this risk is partly mediated by the high emotional demands of the work.

  4. A prospective naturalistic study of 326 panic-agoraphobic patients treated with antidepressants.

    PubMed

    Toni, C; Perugi, G; Frare, F; Mata, B; Vitale, B; Mengali, F; Recchia, M; Serra, G; Akiskal, H S

    2000-07-01

    How far the results of randomized controlled studies apply to everyday care cannot be judged without regular measurements of outcomes in daily practice. We report on systematic data from a 3-year naturalistic prospective study on panic disorder-agoraphobic (PDA) patients treated with antidepressants in a setting of routine clinical practice. Our aim is to describe the evolution of PDA in relation to the treatments employed, and to explore demographic and clinical characteristics that might be predictive of outcome. 326 DSM-III-R PDA patients treated with antidepressants in a setting of routine clinical practice were included in a 3-year naturalistic prospective study. We utilized structured and semi-structures instruments, including the Structured Clinical Interview for Diagnosis and the Longitudinal Interview Follow-up Examination. The main antidepressants used were imipramine (39%), clomipramine (28.5%) and paroxetine (23.3%); only 9% of patients received other antidepressants. 147 patients (45.1%) stayed on medication throughout the entire period of the follow-up. Of those who interrupted the treatment, 38% stayed in remission. The probability of achieving at least one remission during the 3-year follow-up period was 96.5% for PD and 95.9% for Agoraphobia. Relapses after a period of at least 2 months of complete remission were also common, and the probability of presenting at least one relapse during the 3-years follow-up period was 67.1% for PD and 39% for Agoraphobia. The longest period of remission of PD is associated with low severity, medium-lasting course in patients with an onset of the illness in young adulthood. Less severe agoraphobia associated with moderately severe panic attacks appears to confer a better control of phobic behavior. All three major drugs were reasonably well tolerated (only 9% dropped out because of side effects), with sexual dysfunction and increased appetite being the most common side effects at the last evaluation; in the first

  5. Sales of antidepressants, suicides and hospital admissions for depression in Veneto Region, Italy, from 2000 to 2005: an ecological study.

    PubMed

    Guaiana, Giuseppe; Andretta, Margherita; Griez, Eric; Biancosino, Bruno; Grassi, Luigi

    2011-09-30

    Increased prescription of antidepressants has been consistently associated with a decrease in suicide rates in several countries. The aim of this study is to explore antidepressant consumption, suicide rates and admission for depression in the Veneto Region, Italy, in order to see whether the same pattern could be detected. Data from the Italian Ministry of Health (admissions for depression), the Pharmacy Service of a Local Health Unit (antidepressant prescribing) and from the Epidemiological System of the Veneto region (suicide rates) were collected from 2000 to 2005 for the Veneto region. Suicide rates did not show any marked increase but were stable in males and females. Antidepressant prescribing increased exponentially over the period examined, whilst admissions for depression markedly decreased. The trend for an exponential increase in antidepressant prescribing in the Veneto region is shared with other countries and locales. It is possible that the increase in antidepressant prescribing might be associated with earlier treatment of depression, thus decreasing the likelihood of aggravation of depression.

  6. Learning to experience side effects after antidepressant intake - Results from a randomized, controlled, double-blind study.

    PubMed

    Rheker, Julia; Winkler, Alexander; Doering, Bettina K; Rief, Winfried

    2017-02-01

    Side effects play a key role in patients' failure to take antidepressants. There is evidence that verbal suggestions and informed consent elicit expectations that can in turn trigger the occurrence of side effects. Prior experience or learning mechanisms are also assumed to contribute to the development of side effects, although their role has not been thoroughly investigated. In this study, we examined whether an antidepressant's side effects can be learned via Pavlovian conditioning. Participants (n = 39) were randomly allocated to one of two groups and were exposed to a classical conditioning procedure. During acquisition, 19 participants received amitriptyline and 20 participants received a placebo pill. Pills were taken for four nights together with a novel-tasting drink. After a washout phase, both groups received a placebo pill together with the novel-tasting drink (evocation). Side effects were assessed via the Generic Assessment of Side Effects Scale prior to acquisition (baseline), after acquisition, and after evocation. A score of antidepressant-specific side effects was calculated. Participants taking amitriptyline reported significantly more antidepressant-specific side effects after acquisition compared to both baseline and the placebo group. After evocation, participants who underwent the conditioning procedure with amitriptyline reported significantly more antidepressant-specific side effects than those who never received amitriptyline, even though both groups received a placebo. Our results indicate that antidepressant side effects can be learned using a conditioning paradigm and evoked via a placebo pill when applied with the same contextual factors as the verum.

  7. Long-term antidepressant use: a qualitative study on perspectives of patients and GPs in primary care.

    PubMed

    Bosman, Renske C; Huijbregts, Klaas M; Verhaak, Peter Fm; Ruhé, Henricus G; van Marwijk, Harm Wj; van Balkom, Anton Jlm; Batelaan, Neeltje M

    2016-10-01

    Antidepressant use is often prolonged in patients with anxiety and/or depressive disorder(s) compared with recommendations in treatment guidelines to discontinue after sustained remission. To unravel the motivations of patients and GPs causing long-term antidepressant use and to gain insight into possibilities to prevent unnecessary long-term use. Qualitative study using semi-structured, in-depth interviews with patients and GPs in the Netherlands. Patients with anxiety and/or depressive disorder(s) (n = 38) and GPs (n = 26) were interviewed. Innovatively, the interplay between patients and their GPs was also investigated by means of patient-GP dyads (n = 20). The motives and barriers of patients and GPs to continue or discontinue antidepressants were related to the availability of supportive guidance during discontinuation, the personal circumstances of the patient, and considerations of the patient or GP. Importantly, dyads indicated a large variation in policies of general practices around long-term use and continuation or discontinuation of antidepressants. Dyads further indicated that patients and GPs seemed unaware of each other's (mismatching) expectations regarding responsibility to initiate discussing continuation or discontinuation. Although motives and barriers to antidepressant continuation or discontinuation were related to the same themes for patients and GPs, dyads indicated discrepancies between them. Discussion between patients and GPs about antidepressant use and continuation or discontinuation may help clarify mutual expectations and opinions. Agreements between a patient and their GP can be included in a patient-tailored treatment plan. © British Journal of General Practice 2016.

  8. Antidepressant use and risk of coronary heart disease: meta-analysis of observational studies

    PubMed Central

    Oh, Seung-Won; Kim, Joonseok; Myung, Seung-Kwon; Hwang, Seung-Sik; Yoon, Dae-Hyun

    2014-01-01

    Aims Our goal was to evaluate the association between antidepressant use and the risk of coronary heart disease (CHD) among subjects with no history of coronary heart disease. Methods A search of Medline, EMBASE, PsycINFO and the Cochrane Library was performed in January 2013. Two authors independently reviewed and selected eligible observational studies, based on predetermined selection criteria. Pooled relative risks (RRs) with confidence intervals (CIs) were calculated using random-effects or fixed-effects models. Results Sixteen observational studies (seven case–control studies and nine cohort studies) were included in the final analysis. There was no association between selective serotonin reuptake inhibitor use and the risk of CHD overall [odds ratio (OR), 0.93; 95% CI, 0.65–1.33] or in subgroup meta-analysis of case–control studies (OR, 0.91; 95% CI, 0.60–1.37) and cohort studies (RR, 0.96; 95% CI, 0.59–1.55). The use of tricyclic antidepressant was associated with an increased risk of CHD overall (OR, 1.51; 95% CI, 1.07–2.12), but it was observed only in case–control studies (OR, 1.56; 95% CI, 1.24–1.96) and low-quality studies (OR, 1.49; 95% CI, 1.20–1.85) in the subgroup meta-analyses. Conclusions This meta-analysis of observational studies in subjects with no history of CHD suggests that neither selective serotonin reuptake inhibitor nor tricyclic antidepressant use is associated with an increased risk of CHD. PMID:24646010

  9. Prevalence of depression, quality of life and antidepressant treatment in the Danish General Suburban Population Study.

    PubMed

    Ellervik, Christina; Kvetny, Jan; Christensen, Kaj Sparle; Vestergaard, Mogens; Bech, Per

    2014-10-01

    The Danish General Suburban Population Study (GESUS), the objective of which is to facilitate epidemiological and genetic research, has included the Major Depression Inventory (MDI) and the WHO-Five Well-Being Index (WHO-5) among the medical health questionnaires. We were thus in a position to compare the 2-week prevalence of ICD-10 depression in the period from 2010 to 2012 with our previous Danish general population study from 2003, in which the MDI was also included. The aim of our analysis was not only to evaluate the point prevalence of ICD-10 depression but also to describe the prevalence of antidepressants received by the respondents in the GESUS study and the correspondence to their subjective well-being on the WHO-5 questionnaire. To evaluate the validity (scalability) of the MDI and the WHO-5 in the GESUS study we performed the non-parametric Mokken analysis. The scalability of the MDI and the WHO-5 was quite acceptable. In total, 14,787 respondents were available from a response rate of 50%. The 2-week prevalence of ICD-10 depression was 2.3%, which is rather similar to the 2.8% in our 2003 study. The rate of people receiving antidepressants increased consistently with increasing severity of ICD-10 depression. This study has confirmed that the use of the MDI to obtain an ICD-10 depression diagnosis gives rather conservative estimates of the 2-week prevalence of depression in the Danish general population. The prescription of antidepressants depends on the severity of the ICD-10 depression diagnosis.

  10. The monitoring of longer term prescriptions of antidepressants: observational study in a primary care setting.

    PubMed

    Sinclair, Jennifer E; Aucott, Lorna S; Lawton, Kenneth; Reid, Ian C; Cameron, Isobel M

    2014-08-01

    There is little evidence to guide the frequency of review for patients taking antidepressants in the longer term. To measure the frequency with which patients on longer term courses of antidepressants have their treatment monitored in primary care and to identify patient characteristics associated with the frequency of monitoring. A cohort of patients who were receiving antidepressants continuously for at least two years was identified from four general practices. Data were collected from patients' general medical records. The dates of all GP consultations and whether they included a documented review of antidepressant therapy were recorded, along with patient characteristics hypothesized to influence the frequency of monitoring. The frequency of antidepressant review consultations and proportion of participants being reviewed during a specific year of antidepressant therapy decreased with increasing year of antidepressant therapy. Individuals who receive antidepressants for an overt mental health reason; undergo more dose and drug changes; and who are referred to the community mental health team have their antidepressant therapy reviewed more often during the first five years of antidepressant therapy. As many patients on longer term courses of antidepressants are not being appropriately reviewed, a 'chronic disease management approach' to depression in primary care is advocated. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. Blonanserin – A Novel Antianxiety and Antidepressant Drug? An Experimental Study

    PubMed Central

    Limaye, Ramchandra Prabhakar; Patil, Aditi Nitin

    2016-01-01

    Introduction Many psychiatric disorders show signs and symptoms of anxiety and depression. A drug with both, effects and lesser adverse effects is always desired. Blonanserin is a novel drug with postulated effect on anxiety and depression. Aim The study was aimed to evaluate the effect of Blonanserin on anxiety and depression in animal models. Materials and Methods By using elevated plus maze test and forced swimming test, the antianxiety and antidepressant effects were evaluated. Animal ethics protocols were followed strictly. Total 50 rats (10 rats per group) were used for each test. As a control drug diazepam and imipramine were used in elevated plus maze and forced swimming test respectively. Blonanserin was tested for 3 doses 0.075, 0.2 and 0.8mg. These doses were selected from previous references as well as by extrapolating human doses. Results This study showed an antianxiety effect of Blonanserin comparable to diazepam, which was statistically significant. Optimal effect was observed with 0.075mg, followed by 0.2 and 0.8mg. It also showed an antidepressant effect which was statistically significant. Optimal effect was observed at 0.2mg dose. Conclusion The results showed that at a dose range of 0.075 and 0.2mg Blonanserin has potential to exert an adjuvant antianxiety and antidepressant activity in animal models. In order to extrapolate this in patient, longer clinical studies with comparable doses should be planned. The present study underlines potential of Blonanserin as a novel drug for such studies. PMID:27790460

  12. Use of antidepressive agents as a possibility in the management of periodontal diseases: A systematic review of experimental studies.

    PubMed

    Muniz, Francisco Wilker Mustafa Gomes; Melo, Iracema Matos; Rösing, Cassiano Kuchenbecker; de Andrade, Geanne Matos; Martins, Ricardo Souza; Moreira, Maria Mônica Studart Mendes; Carvalho, Rosimary de Sousa

    2017-09-01

    Antidepressant agents have anti-inflammatory functions that could be interesting as adjuvants in periodontal therapy. The aim of the present study was to analyze the effect of antidepressive drugs in the management of periodontal disease. The MEDLINE, Scopus, Embase, LILACS, and SciELO databases were searched. To be included, the studies had to be experimental studies; randomized, controlled; double-blinded; or blinded studies. A total of 565 articles were initially searched, of which five were selected for the systematic review. All studies used rats, and three different drugs were evaluated: tianeptine, venlafaxine, and fluoxetine. Two of these studies evaluated the effect of antidepressive agents in rats submitted to both ligature-induced periodontitis and depression models, showing that depressive rats had greater alveolar bone loss (ABL). Only the venlafaxine study was not able to find any significant ABL reduction in the group that used this antidepressive drug. The other four studies showed statistically-significant differences, favoring the group with the antidepressant agent. Treatments that are able to modulate the brain-neuroendocrine-immune system could be used as an adjuvant to periodontal disease management. However, studies on humans and animals are scarce, limiting the conclusion of a positive effect in the present systematic review. © 2017 John Wiley & Sons Australia, Ltd.

  13. Curcumin as an add-on to antidepressive treatment: a randomized, double-blind, placebo-controlled, pilot clinical study.

    PubMed

    Bergman, Joseph; Miodownik, Chanoch; Bersudsky, Yuly; Sokolik, Shmuel; Lerner, Paul P; Kreinin, Anatoly; Polakiewicz, Jacob; Lerner, Vladimir

    2013-01-01

    Depression is a widespread mental disorder in which nearly half of the affected people have recurrent symptoms. Drug combinations may produce cumulative adverse effects, especially in elderly and physically ill patients. It was demonstrated that curcumin possesses antidepressive activity in various animal models of depression, and a combination of curcumin with some antidepressants potentiates the antidepressive effect of these agents. We sought to evaluate the efficacy of curcumin as an antidepressive agent in a combination with other antidepressants in patients with major depression. Forty patients with a first episode of depression participated in a 5-week, double-blind, randomized, placebo-controlled study. The subjects were treated with either 500-mg/d curcumin or placebo together with antidepressants (escitalopram or venlafaxine) during August 2010 until June 2011. The outcome measures were Clinical Global Impression-Severity Scale, Hamilton Depression Rating Scale, and Montgomery-Asberg Depression Rating Scale. Analysis of variance showed significant positive changes in both groups from baseline to the end of the study in all scales of measurement. These changes became significant from the first visit after 7 days of treatment. There was no difference between curcumin and placebo, which means negative results. However, the patients in the curcumin group demonstrated a trend to a more rapid relief of depressive symptoms in comparison to those in the placebo group. None of the patients complained of any adverse effect during the study. Although there is no definitive proof that curcumin can induce an earlier beneficial effect of antidepressive agents, it seems like an extended study is needed to prove it, using higher therapeutic doses of curcumin.

  14. Bridging intravenous-intra-arterial rescue strategy increases recanalization and the likelihood of a good outcome in nonresponder intravenous tissue plasminogen activator-treated patients: a case-control study.

    PubMed

    Rubiera, Marta; Ribo, Marc; Pagola, Jorge; Coscojuela, Pilar; Rodriguez-Luna, David; Maisterra, Olga; Ibarra, Bernardo; Piñeiro, Socorro; Meler, Pilar; Romero, Francisco J; Alvarez-Sabin, Jose; Molina, Carlos A

    2011-04-01

    Safety and efficacy of the "bridging therapy" (intra-arterial [IA] reperfusion rescue for nonresponder intravenous [IV] tissue plasminogen activator [tPA]-treated patients) is a matter of debate. Our aim was to compare IV and IV-IA thrombolysis using a case-control approach. Consecutive patients with proximal intracranial occlusion who received IA reperfusion procedures after unsuccessful IV tPA (lack of clinical improvement and arterial recanalization 1 hour after tPA bolus) were studied (IV-IA group). They were compared with occluded vessel, clot location, stroke severity, and time to treatment-matched 1 to 2 historical patients from our prospective IV tPA database with persistent occlusion 1 hour after IV tPA (IV-NR group). Arterial occlusion and recanalization were assessed with transcranial Doppler. Clinical evaluation was assessed by National Institutes of Health Stroke Scale at baseline, 24 hours, and at discharge. Symptomatic intracranial hemorrhage was defined according to the National Institute of Neurological Disorders and Stroke trial. Functional evaluation was determined by modified Rankin Scale, being functional independency defined by modified Rankin Scale score ≤2. Forty-two IV-IA patients were compared with 84 matched IV-NR. Mean age was 71.5±2.9 years, 58 (46%) were women, and baseline median National Institutes of Health Stroke Scale score was 20 (interquartile range, 5). Mean time from symptoms to IV tPA was 176.9±113 minutes. On transcranial Doppler, complete recanalization was significantly higher in IV-IA than control subjects (12 hours: 45.2% versus 18.1%, P=0.002; 24 hours: 46.3% versus 25.3%, P=0.016) with nonsignificant better clinical evolution at 24 hours (40.5% versus 30.1%, P=0.169) and discharge (52.5% versus 39.5%, P=0.123). Symptomatic intracranial hemorrhage was similar (IV-IA 11.9% versus IV-NR 6%, P=0.205). Mortality at 3 months was 50% in the IV-IA group and 35.8% in the IV-NR (P=0.154). Forty percent of IV-IA patients were

  15. Antidepressant Use and Recurrent Falls in Community-Dwelling Older Adults: Findings From the Health ABC Study

    PubMed Central

    Marcum, Zachary A.; Perera, Subashan; Thorpe, Joshua M.; Switzer, Galen E.; Castle, Nicholas G.; Strotmeyer, Elsa S.; Simonsick, Eleanor M.; Ayonayon, Hilsa N.; Phillips, Caroline L.; Rubin, Susan; Zucker-Levin, Audrey R.; Bauer, Douglas C.; Shorr, Ronald I.; Kang, Yihuang; Gray, Shelly L.; Hanlon, Joseph T.

    2016-01-01

    Background Few studies have compared the risk of recurrent falls across various antidepressant agents—using detailed dosage and duration data—among community-dwelling older adults, including those who have a history of a fall/fracture. Objective To examine the association of antidepressant use with recurrent falls, including among those with a history of falls/fractures, in community-dwelling elders. Methods This was a longitudinal analysis of 2948 participants with data collected via interview at year 1 from the Health, Aging and Body Composition study and followed through year 7 (1997-2004). Any antidepressant medication use was self-reported at years 1, 2, 3, 5, and 6 and further categorized as (1) selective serotonin reuptake inhibitors (SSRIs), (2) tricyclic antidepressants, and (3) others. Dosage and duration were examined. The outcome was recurrent falls (≥2) in the ensuing 12-month period following each medication data collection. Results Using multivariable generalized estimating equations models, we observed a 48% greater likelihood of recurrent falls in antidepressant users compared with nonusers (adjusted odds ratio [AOR] = 1.48; 95% CI = 1.12-1.96). Increased likelihood was also found among those taking SSRIs (AOR = 1.62; 95% CI = 1.15-2.28), with short duration of use (AOR = 1.47; 95% CI = 1.04-2.00), and taking moderate dosages (AOR = 1.59; 95% CI = 1.15-2.18), all compared with no antidepressant use. Stratified analysis revealed an increased likelihood among users with a baseline history of falls/fractures compared with nonusers (AOR = 1.83; 95% CI = 1.28-2.63). Conclusion Antidepressant use overall, SSRI use, short duration of use, and moderate dosage were associated with recurrent falls. Those with a history of falls/fractures also had an increased likelihood of recurrent falls. PMID:27066988

  16. Antidepressant use and associations with psychosocial work characteristics. A comparative study of Swedish and Danish gainfully employed.

    PubMed

    Magnusson Hanson, Linda L; Madsen, Ida E H; Westerlund, Hugo; Theorell, Töres; Burr, Hermann; Rugulies, Reiner

    2013-07-01

    Although depression is common, prevalence estimates of antidepressant use among the workforce and undisputed evidence relating psychosocial work characteristics to depression is scarce. This study cross-sectionally assesses the prevalence of antidepressant use among employed in Sweden and Denmark and prospectively examines associations between work characteristics and antidepressant use. Data on work demands, influence and learning possibilities was collected 2005-2006 from two representative samples of employed aged 20-59 years from Sweden (n=4351) and Denmark (n=8064) and linked to purchases of antidepressants through national prescription drug registries. Standardized 12-month prevalences were calculated. Cox regressions on work characteristics and incident use were performed separately and estimates pooled. Employed Swedish residents had higher standardized prevalence than Danish, 6.0% compared to 5.0%. Working fast and conflicting demands were associated with incident use when estimates were pooled, but adjustment for baseline health attenuated these estimates. Emotionally disturbing situations were related to any incident use, and more strongly to use >179 defined daily dosages/year, even after adjustment for various covariates. Statistics based on national prescription drug registries are influenced by, e.g., treatment seeking behaviours and other reasons for prescription than depression. Selective drop-out may also affect prevalence estimates. The study indicates that use of antidepressants among the workforce is relatively high and that employed Swedish residents had higher prevalence of antidepressant use than Danish. Relationships between work characteristics and antidepressant use were, however, similar with emotional demands showing the strongest association, indicating that particular groups of employees may be at increased risk. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Last-observation-carried-forward imputation method in clinical efficacy trials: review of 352 antidepressant studies.

    PubMed

    Woolley, Stephen B; Cardoni, Alex A; Goethe, John W

    2009-12-01

    To determine the prevalence, over 40 years, of using the last-observation-carried-forward (LOCF) imputation method in clinical trials, the association between use of LOCF and how the trials were conducted, and the extent of information about attrition and LOCF use in published reports. Retrospective analysis of the reports of randomized antidepressant efficacy trials published over a 40-year period (1965-2004). MEDLINE database, Cochrane reviews, reference- and bibliography-based manual search, and publication list services. A total of 352 trials met the following criteria for analysis: antidepressant comparative efficacy trial, randomized design, patients with major depressive disorder, English-language article, published during 1965-2004, and first report of a trial. Design, attrition, and data analysis characteristics were recorded by investigators and trained assistants. Analyses included descriptive statistics of the trial size, duration, and number of patients who dropped out in LOCF versus non-LOCF studies, as well as the extent to which dropouts and the potential bias associated with attrition was discussed in the published report. The frequency of published antidepressant clinical trials increased from less than 1 trial/year (1965-1974) to 19 trials/year (1990-1994). Trials using the LOCF method were significantly larger than non-LOCF trials (p<0.01), and the proportion of subjects dropping out was significantly greater (p<0.05) in LOCF versus non-LOCF trials. The proportion of subjects dropping out remained relatively constant over time (approximately 30%) but was significantly greater among LOCF (30.9%) than non-LOCF (28.8%) trials (p<0.01). The LOCF study articles were more likely to report dropouts, but only 7% of these articles reported outcomes recorded for subjects before they dropped out. Less than 16% of articles discussed bias associated with dropouts, 6.8% discussed the direction of bias, and only about 2% suggested the magnitude of the bias

  18. Living alone and antidepressant medication use: a prospective study in a working-age population.

    PubMed

    Pulkki-Råback, Laura; Kivimäki, Mika; Ahola, Kirsi; Joutsenniemi, Kaisla; Elovainio, Marko; Rossi, Helena; Puttonen, Sampsa; Koskinen, Seppo; Isometsä, Erkki; Lönnqvist, Jouko; Virtanen, Marianna

    2012-03-23

    An increasing proportion of the population lives in one-person households. The authors examined whether living alone predicts the use of antidepressant medication and whether socioeconomic, psychosocial, or behavioral factors explain this association. The participants were a nationally representative sample of working-age Finns from the Health 2000 Study, totaling 1695 men and 1776 women with a mean age of 44.6 years. In the baseline survey in 2000, living arrangements (living alone vs. not) and potential explanatory factors, including psychosocial factors (social support, work climate, hostility), sociodemographic factors (occupational grade, education, income, unemployment, urbanicity, rental living, housing conditions), and health behaviors (smoking, alcohol use, physical activity, obesity), were measured. Antidepressant medication use was followed up from 2000 to 2008 through linkage to national prescription registers. Participants living alone had a 1.81-fold (CI = 1.46-2.23) higher purchase rate of antidepressants during the follow-up period than those who did not live alone. Adjustment for sociodemographic factors attenuated this association by 21% (adjusted OR = 1.64, CI = 1.32-2.05). The corresponding attenuation was 12% after adjustment for psychosocial factors (adjusted OR = 1.71, CI = 1.38-2.11) and 9% after adjustment for health behaviors (adjusted OR = 1.74, CI = 1.41-2.14). Gender-stratified analyses showed that in women the greatest attenuation was related to sociodemographic factors and in men to psychosocial factors. These data suggest that people living alone may be at increased risk of developing mental health problems. The public health value is in recognizing that people who live alone are more likely to have material and psychosocial problems that may contribute to excess mental health problems in this population group.

  19. Diabetes incidence associated with depression and antidepressants in the Melbourne Longitudinal Studies on Healthy Ageing (MELSHA).

    PubMed

    Atlantis, Evan; Browning, Colette; Sims, Jane; Kendig, Hal

    2010-07-01

    Diabetes may be associated with depression and antidepressant medication (ADM) use, but published findings remain equivocal. The authors' aimed to determine the risk of diabetes incidence associated with baseline depression exposures (symptoms and/or ADM use). A prospective cohort study was conducted in a regionally representative sample of non-institutionalised older Australian people (N = 1000, aged 65 + year), who were followed up biennially between 1994 and 2004 (attrition was approximately 24%). Analyses excluded participants for prevalent diabetes at baseline, determined by self-report or specific medications. Diabetes incidence was ascertained by first self-report at any follow-up wave. Depression exposures (baseline predictors) were defined by the Psychogeriatric Assessment Scales (PAS) depression scale and ADM use, and classified as: (1) 'symptomatic' (PAS score 5+); (2) 'ADM use'; (3) 'symptomatic or ADM use'; (4) 'symptomatic and no ADM use'; (5) 'asymptomatic (PAS score <5) and ADM use' and (6) 'symptomatic and ADM use'. Covariates were demographic, lifestyle, functional health and chronic disease factors. Cox regressions were used to determined hazard ratios with 95% confidence intervals (HR [95% CI]) for diabetes incidence according to depression exposures, adjusted for significant covariates. Baseline response rate was 70.3%. Depression predictors of diabetes incidence were 'symptomatic' (2.29 [1.28,4.10]), 'symptomatic or ADM use' (2.13 [1.32,3.44]) and 'symptomatic and no ADM use' (2.38 [1.28,4.45]), after adjustment for significant covariates. Being asymptomatic was not a protective factor among those prescribed antidepressants. Older people with depressive symptoms are at least twice more likely to develop diabetes than those without depressive symptoms, regardless of antidepressants. (c) 2009 John Wiley & Sons, Ltd.

  20. Antidepressants in Parkinson's disease. Recommendations by the movement disorder study group of the Neurological Association of Madrid.

    PubMed

    Peña, E; Mata, M; López-Manzanares, L; Kurtis, M; Eimil, M; Martínez-Castrillo, J C; Navas, I; Posada, I J; Prieto, C; Ruíz-Huete, C; Vela, L; Venegas, B

    2016-03-19

    Although antidepressants are widely used in Parkinson's disease (PD), few well-designed studies to support their efficacy have been conducted. These clinical guidelines are based on a review of the literature and the results of an AMN movement disorder study group survey. Evidence suggests that nortriptyline, venlafaxine, paroxetine, and citalopram may be useful in treating depression in PD, although studies on paroxetine and citalopram yield conflicting results. In clinical practice, however, selective serotonin reuptake inhibitors are usually considered the treatment of choice. Duloxetine may be an alternative to venlafaxine, although the evidence for this is less, and venlafaxine plus mirtazapine may be useful in drug-resistant cases. Furthermore, citalopram may be indicated for the treatment of anxiety, atomoxetine for hypersomnia, trazodone and mirtazapine for insomnia and psychosis, and bupropion for apathy. In general, antidepressants are well tolerated in PD. However, clinicians should consider the anticholinergic effect of tricyclic antidepressants, the impact of serotonin-norepinephrine reuptake inhibitors on blood pressure, the extrapyramidal effects of antidepressants, and any potential interactions between monoamine oxidase B inhibitors and other antidepressants. Copyright © 2016 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  1. Evening salivary alpha-amylase, major depressive disorder, and antidepressant use in the Netherlands Study of Depression and Anxiety (NESDA).

    PubMed

    Veen, Gerthe; Giltay, Erik J; Licht, Carmilla M M; Vreeburg, Sophie A; Cobbaert, Christa M; Penninx, Brenda W J H; Zitman, Frans G

    2013-06-30

    Salivary alpha-amylase (sAA) may be a suitable index for sympathetic activity and dysregulation of the autonomic nervous system. The relationship between antidepressants and depression with sAA levels was studied, since antidepressants were previously shown to have a profound impact on heart rate variability as an ANS indicator. Data are from 1692 participants of the Netherlands Study of Depression and Anxiety (NESDA) who were recruited from the community, general practice, and specialized mental health care. Differences in evening sAA levels were examined between patient groups (i.e., 752 current major depressive disorder [MDD], 611 remitted MDD, and 329 healthy controls) and between 46 tricyclic antidepressant (TCA) users, 307 selective serotonin reuptake inhibitor (SSRI) users, 97 users of another antidepressant, and 1242 non-users. Each participant sampled twice at 22.00h and 23.00h. In multivariable analysis, there was a trend over the three groups with increasing sAA levels from controls to remitted MDD to current MDD that approached significance. Furthermore, in comparison to non-users of antidepressants, TCA rather than SSRI users showed higher sAA levels, that persisted after multivariable adjustment. The present study shows that higher evening sAA levels in depressed patients, indicative of an increased sympathetic activity, may be induced by TCAs.

  2. Risk analysis of use of different classes of antidepressants on subsequent dementia: A nationwide cohort study in Taiwan.

    PubMed

    Then, Chee-Kin; Chi, Nai-Fang; Chung, Kuo-Hsuan; Kuo, Lynn; Liu, Kao-Hui; Hu, Chaur-Jong; Shen, Shing-Chuan; Lin, Yen-Kuang

    2017-01-01

    Depression and dementia are common mental health problems and are associated in several ways. Early-life depression is associated with increased risk of later life dementia, and depression can present as a preclinical symptom or consequence of dementia. Despite the plausible relationship between these two clinical entities, the potential association between antidepressant medication and dementia has rarely been investigated. We conducted a 9-year retrospective analysis of Taiwan's National Health Insurance Research Database (NHIRD), enrolling 5819 cases who had received prescriptions of antidepressants between 2003 and 2006, and 23,276 (with ratio of 1:4) age, sex, and index date-matched controls. The hazard ratio (HR) of dementia among antidepressant users with depression was 2.42 (95% confidence interval (CI): 1.15-5.10), for those without depression was 4.05 (95% CI: 3.19-5.15), compared to antidepressant non-users respectively. Among the 6 classes of common antidepressants used in Taiwan, the adjusted HRs were 3.66 (95% CI: 2.62-5.09) for SSRIs, 4.73 (95% CI: 2.54-8.80) for SNRI, 3.26 (95% CI: 2.30-4.63) for TCAs, 6.62 (95% CI: 3.34-13.13) for TeCA, 4.94 (95% CI: 2.17-11.24) for MAOI, and 4.48 (95% CI: 3.13-6.40) for SARI. Furthermore, the multivariate analysis result showed that the adjusted HRs of cumulative defined daily doses (cDDDs) were 3.74 (95% CI: 2.91-4.82), 3.73 (95% CI: 2.39-5.80) and 5.22 (95% CI: 3.35-8.14) for those who had cDDDs of <90, 90-180 and >180 compared to those who had taken no antidepressant medication. This is a retrospective study based on secondary data, hence, we could not claim causality between antidepressant medication and dementia. However, a potential association between antidepressant and occurrence of dementia after controlling for the status of depression was observed. Lack of patients' data about smoking status and body mass index in NHIRD, which are considered related to dementia, was also a limitation in this study. In

  3. Pharmacogenomic study of side-effects for antidepressant treatment options in STAR*D.

    PubMed

    Clark, S L; Adkins, D E; Aberg, K; Hettema, J M; McClay, J L; Souza, R P; van den Oord, E J C G

    2012-06-01

    Understanding individual differences in susceptibility to antidepressant therapy side-effects is essential to optimize the treatment of depression. We performed genome-wide association studies (GWAS) to search for genetic variation affecting the susceptibility to side-effects. The analysis sample consisted of 1439 depression patients, successfully genotyped for 421K single nucleotide polymorphisms (SNPs), from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Outcomes included four indicators of side-effects: general side-effect burden, sexual side-effects, dizziness and vision/hearing-related side-effects. Our criterion for genome-wide significance was a prespecified threshold ensuring that, on average, only 10% of the significant findings are false discoveries. Thirty-four SNPs satisfied this criterion. The top finding indicated that 10 SNPs in SACM1L mediated the effects of bupropion on sexual side-effects (p = 4.98 × 10(-7), q = 0.023). Suggestive findings were also found for SNPs in MAGI2, DTWD1, WDFY4 and CHL1. Although our findings require replication and functional validation, this study demonstrates the potential of GWAS to discover genes and pathways that could mediate adverse effects of antidepressant medication.

  4. Antidepressant medicine use and risk of developing diabetes during the diabetes prevention program and diabetes prevention program outcomes study.

    PubMed

    Rubin, Richard R; Ma, Yong; Peyrot, Mark; Marrero, David G; Price, David W; Barrett-Connor, Elizabeth; Knowler, William C

    2010-12-01

    To assess the association between antidepressant medicine use and risk of developing diabetes during the Diabetes Prevention Program (DPP) and Diabetes Prevention Program Outcomes Study (DPPOS). DPP/DPPOS participants were assessed for diabetes every 6 months and for antidepressant use every 3 months in DPP and every 6 months in DPPOS for a median 10.0-year follow-up. Controlled for factors associated with diabetes risk, continuous antidepressant use compared with no use was associated with diabetes risk in the placebo (adjusted hazard ratio 2.34 [95% CI 1.32-4.15]) and lifestyle (2.48 [1.45-4.22]) arms, but not in the metformin arm (0.55 [0.25-1.19]). Continuous antidepressant use was significantly associated with diabetes risk in the placebo and lifestyle arms. Measured confounders and mediators did not account for this association, which could represent a drug effect or reflect differences not assessed in this study between antidepressant users and nonusers.

  5. Pregabalin augmentation of antidepressants in patients with accident-related posttraumatic stress disorder: an open label pilot study.

    PubMed

    Pae, Chi-Un; Marks, David M; Han, Changsu; Masand, Prakash S; Patkar, Ashwin A

    2009-01-01

    This study evaluated the efficacy of pregabalin augmentation of antidepressant treatment in patients with posttraumatic stress disorder (PTSD). Nine patients meeting Diagnostic and Statistical Manual, fourth edition criteria for PTSD who were on stable doses of antidepressants were treated open label with flexibly dosed pregabalin for 6 weeks. All patients were assessed with the Short PTSD Rating Interview, Montgomery-Asberg Depression Rating Scale, Patient Global Impression-severity, Visual Analog Scale-pain, and Sheehan Disability Scale at baseline and weeks 2, 4, and 6. Significant reductions were observed in all effectiveness measures from week 4 to the end of the study. In particular, the numerical improvement of the Visual Analog Scale-pain score was most robust (-53.4%, P=0.007). Pregabalin augmentation was effective and well tolerated during the study. Our findings warrant adequately powered, placebo-controlled clinical trials to confirm the usefulness of pregabalin augmentation of antidepressants in patients with PTSD.

  6. Using Multiple Imputation to Assign Pesticide Use for Non-Responders in the Follow-Up Questionnaire in the Agricultural Health Study

    EPA Science Inventory

    The Agricultural Health Study (AHS), a large prospective cohort, was designed to elucidate associations between pesticide use and other agricultural exposures and health outcomes. The cohort includes 57,310 pesticide applicators who were enrolled between 1993 and 1997 in Iowa and...

  7. Using Multiple Imputation to Assign Pesticide Use for Non-Responders in the Follow-Up Questionnaire in the Agricultural Health Study

    EPA Science Inventory

    The Agricultural Health Study (AHS), a large prospective cohort, was designed to elucidate associations between pesticide use and other agricultural exposures and health outcomes. The cohort includes 57,310 pesticide applicators who were enrolled between 1993 and 1997 in Iowa and...

  8. A controlled study of the antidepressant efficacy and side effects of (-)-deprenyl. A selective monoamine oxidase inhibitor.

    PubMed

    Mann, J J; Aarons, S F; Wilner, P J; Keilp, J G; Sweeney, J A; Pearlstein, T; Frances, A J; Kocsis, J H; Brown, R P

    1989-01-01

    Monoamine oxidase (MAO) inhibitors are effective antidepressants whose use is limited because of unwanted side effects and the possibility of a tyramine-induced hypertensive crisis (cheese reaction). (-)-Deprenyl (the official nonproprietary name for this substance is selegiline), a selective MAO type B inhibitor, may be safer and have fewer side effects, but its antidepressant efficacy is uncertain. A double-blind placebo-controlled study was carried out in depressed outpatients who were treated with (-)-deprenyl in an MAO type B selective dose range and at a higher nonselective dose range. (-)-Deprenyl did not have a statistically significant antidepressant effect after three weeks of treatment at doses of 10 mg/d. However, after six weeks and at higher doses (averaging about 30 mg/d for the second three weeks), (-)-deprenyl was superior to placebo in antidepressant effect with a positive response rate of 50% vs 13.6% and with a 41% reduction in the Hamilton Depression Rating Scale mean score vs 10% in the placebo-treated group. No hypertensive crises were seen. The rate of occurrence of side effects with (-)-deprenyl was no greater than with placebo. It was concluded that (-)-deprenyl is an effective antidepressant in a dose range where it is distinguished by the absence of many of the side effects typical of nonselective MAO inhibitors.

  9. Prenatal antidepressant use and risk of attention-deficit/hyperactivity disorder in offspring: population based cohort study.

    PubMed

    Man, Kenneth K C; Chan, Esther W; Ip, Patrick; Coghill, David; Simonoff, Emily; Chan, Phyllis K L; Lau, Wallis C Y; Schuemie, Martijn J; Sturkenboom, Miriam C J M; Wong, Ian C K

    2017-05-31

    Objective To assess the potential association between prenatal use of antidepressants and the risk of attention-deficit/hyperactivity disorder (ADHD) in offspring.Design Population based cohort study.Setting Data from the Hong Kong population based electronic medical records on the Clinical Data Analysis and Reporting System.Participants 190 618 children born in Hong Kong public hospitals between January 2001 and December 2009 and followed-up to December 2015.Main outcome measure Hazard ratio of maternal antidepressant use during pregnancy and ADHD in children aged 6 to 14 years, with an average follow-up time of 9.3 years (range 7.4-11.0 years).Results Among 190 618 children, 1252 had a mother who used prenatal antidepressants. 5659 children (3.0%) were given a diagnosis of ADHD or received treatment for ADHD. The crude hazard ratio of maternal antidepressant use during pregnancy was 2.26 (P<0.01) compared with non-use. After adjustment for potential confounding factors, including maternal psychiatric disorders and use of other psychiatric drugs, the adjusted hazard ratio was reduced to 1.39 (95% confidence interval 1.07 to 1.82, P=0.01). Likewise, similar results were observed when comparing children of mothers who had used antidepressants before pregnancy with those who were never users (1.76, 1.36 to 2.30, P<0.01). The risk of ADHD in the children of mothers with psychiatric disorders was higher compared with the children of mothers without psychiatric disorders even if the mothers had never used antidepressants (1.84, 1.54 to 2.18, P<0.01). All sensitivity analyses yielded similar results. Sibling matched analysis identified no significant difference in risk of ADHD in siblings exposed to antidepressants during gestation and those not exposed during gestation (0.54, 0.17 to 1.74, P=0.30).Conclusions The findings suggest that the association between prenatal use of antidepressants and risk of ADHD in offspring can be partially explained by

  10. Reboxetine for ADHD in children non-responders or with poor tolerance to methylphenidate: a prospective long-term open-label study.

    PubMed

    Quintero, Javier; López-Muñoz, Francisco; Alamo, Cecilio; Loro, Mercedes; García-Campos, Natalia

    2010-11-01

    Up to 30% of patients with attention-deficit hyperactivity disorder (ADHD) treated with psychostimulants discontinue the treatment because of intolerance or lack of therapeutic response. Therapeutic alternatives are needed for such patients. In the present case series, we study the effectiveness of reboxetine over a period of 6 months in a sample of 14 children diagnosed with ADHD according to DSM-IV-TR criteria, who had responded only partially or had presented poor tolerance to conventional treatment with methylphenidate. Clinical efficacy was evaluated through the application of the 18-item Attention-Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) and the Clinical Global Impressions-Global Improvement Scale (CGI-I). Percentages of responders (ADHD-RS ≥ 25%) and improvers (CGI-I absolute value < 4) were 90.9 and 72.7%, respectively. No serious side-effects were observed during treatment, the most frequent effects being headaches and insomnia. The initial findings of our study show that reboxetine may constitute an effective tool for long-term treatment of children with ADHD who present poor response or poor tolerance to initial treatment with methylphenidate.

  11. The impact of exposure to antidepressant medications during pregnancy on neonatal outcomes: a review of retrospective database cohort studies.

    PubMed

    Tak, Casey R; Job, Kathleen M; Schoen-Gentry, Katie; Campbell, Sarah C; Carroll, Patrick; Costantine, Maged; Brixner, Diana; Birnbaum, Angela K; Sherwin, Catherine M T

    2017-09-01

    Concerns with prescription antidepressant use in pregnant women have instigated the examination of potential associations between fetal exposure to antidepressant medication and outcomes including preterm delivery, congenital malformations, perinatal and post-natal adverse events, persistent pulmonary hypertension, and mortality. The retrospective cohort model is an often utilized study design. The objective of this review is to evaluate the literature on antidepressant use in pregnancy conducted as retrospective cohorts in national/regional medical, or claims databases that assess neonatal and infant outcomes for agreement between studies, ultimately providing a methodological and outcomes summary for future scientific endeavors. PubMed was searched for literature relating to antidepressant use and infant outcomes from the earliest available date through July 15, 2016. Studies with a retrospective cohort design and conducted in national/regional medical or claims databases were included. Searched outcomes included preterm delivery, congenital malformations, low birth weight, small for gestational age, persistent pulmonary hypertension of the newborn, and other select adverse events comprising low Apgar score (5 min), convulsions/seizures, respiratory distress/problems, fetal mortality, and infant mortality. Of the 784 studies identified, 36 retrospective cohort studies met eligibility criteria. An increase in preterm delivery and respiratory distress/problems and no increase in congenital malformation or fetal and infant death were associated with prenatal use of prescription antidepressants by majority consensus (at least 2/3 [67%] of studies). While consensus indicates that perinatal prescription antidepressant use has consequences for the fetus and infant, there are notable inconsistencies in the literature. More investigations that address prenatal exposure to depression and other important covariates are needed.

  12. Analysis of 23andMe antidepressant efficacy survey data: implication of circadian rhythm and neuroplasticity in bupropion response

    PubMed Central

    Li, Q S; Tian, C; Seabrook, G R; Drevets, W C; Narayan, V A

    2016-01-01

    Genetic predisposition may contribute to the differences in drug-specific, class-specific or antidepressant-wide treatment resistance. Clinical studies with the genetic data are often limited in sample sizes. Drug response obtained from self-reports may offer an alternative approach to conduct a study with much larger sample size. Using the phenotype data collected from 23andMe ‘Antidepressant Efficacy and Side Effects' survey and genotype data from 23andMe's research participants, we conducted genome-wide association study (GWAS) on subjects of European ancestry using four groups of phenotypes (a) non-treatment-resistant depression (n=7795) vs treatment-resistant depression (TRD, n=1311), (b) selective serotonin reuptake inhibitors (SSRI) responders (n=6348) vs non-responders (n=3340), (c) citalopram/escitalopram responders (n=2963) vs non-responders (n=2005), and (d) norepinephrine–dopamine reuptake inhibitor (NDRI, bupropion) responders (n=2675) vs non-responders (n=1861). Each of these subgroups was also compared with controls (n ~ 190 000). The most significant association was from bupropion responders vs non-responders analysis. Variant rs1908557 (P=2.6 × 10−8, OR=1.35) passed the conventional genome-wide significance threshold (P=5 × 10−8) and was located within the intron of human spliced expressed sequence tags in chromosome 4. Gene sets associated with long-term depression, circadian rhythm and vascular endothelial growth factor (VEGF) pathway were enriched in the bupropion analysis. No single-nucleotide polymorphism passed genome-wide significance threshold in other analyses. The heritability estimates for each response group compared with controls were between 0.15 and 0.25, consistent with the known heritability for major depressive disorder. PMID:27622933

  13. Mechanistic Study on the Antidepressant-Like Effect of Danggui-Shaoyao-San, a Chinese Herbal Formula

    PubMed Central

    Huang, Zhen; Mao, Qing-Qiu; Zhong, Xiao-Ming; Li, Zhao-Yi; Qiu, Feng-Mei; Ip, Siu-Po

    2012-01-01

    Danggui-Shaoyao-San (DSS), a famous Chinese herbal formula, has been widely used in the treatment of various diseases. Previous studies have shown that DSS produces antidepressant-like effect in rodents. This study aims to investigate the mechanism(s) underlying the antidepressant-like action of DDS. The results showed that DSS treatment significantly antagonized reserpine-induced ptosis in mice. In addition, DSS treatment significantly increased sucrose consumption in chronic unpredictable stress- (CUS-) treated mice. DSS treatment also markedly attenuated CUS-induced decreases in noradrenaline and dopamine concentrations in mouse brain. Furthermore, DSS treatment significantly reversed CUS-induced increase in serum malondialdehyde (MDA) content and decrease in serum superoxide dismutase (SOD) activity in mice. The results suggest that the antidepressant-like activity of DSS is probably mediated by the modulation of central monoamine neurotransmitter systems and the reduction of oxidative stress. PMID:22924052

  14. Antidepressant sales and the risk for alcohol-related and non-alcohol-related suicide in Finland--an individual-level population study.

    PubMed

    Moustgaard, Heta; Joutsenniemi, Kaisla; Myrskylä, Mikko; Martikainen, Pekka

    2014-01-01

    A marked decline in suicide rates has co-occurred with increased antidepressant sales in several countries but the causal connection between the trends remains debated. Most previous studies have focused on overall suicide rates and neglected differential effects in population subgroups. Our objective was to investigate whether increasing sales of non-tricyclic antidepressants have reduced alcohol- and non-alcohol-related suicide risk in different population subgroups. We followed a nationally representative sample of 950,158 Finnish adults in 1995-2007 for alcohol-related (n = 2,859) and non-alcohol-related (n = 8,632) suicides. We assessed suicide risk by gender and social group according to regional sales of non-tricyclic antidepressants, measured by sold doses per capita, prevalence of antidepressant users, and proportion of antidepressant users with doses reflecting minimally adequate treatment. Fixed-effects Poisson regression models controlled for regional differences and time trends that may influence suicide risk irrespective of antidepressant sales. The number of sold antidepressant doses per capita and the prevalence of antidepressant users were unrelated to male suicide risk. However, one percentage point increase in the proportion of antidepressant users receiving minimally adequate treatment reduced non-alcohol-related male suicide risk by one percent (relative risk 0.987, 95% confidence interval 0.976-0.998). This beneficial effect only emerged among men with high education, high income, and employment, among men without a partner, and men not owning their home. Alcohol-related suicides and female suicides were unrelated to all measures of antidepressant sales. We found little evidence that increase in overall sales or in the prevalence of non-tricyclic antidepressant users would have caused the fall in suicide rates in Finland in 1995-2007. However, the rise in the proportion of antidepressant users receiving minimally adequate treatment, possibly

  15. Barriers and facilitators of adherence to antidepressants among outpatients with major depressive disorder: A qualitative study

    PubMed Central

    Jacob, Sabrina Anne; Tangiisuran, Balamurugan

    2017-01-01

    Background One of the major challenges in treating major depressive disorder (MDD) is patients’ non-adherence to medication. This study aimed to explore the barriers and facilitators of patients’ adherence to antidepressants among outpatients with MDD. Methods Semi-structured and individual in-depth interviews were conducted among patients with MDD who were taking antidepressants, in the psychiatric clinic of a government-run hospital in Malaysia. Participants were purposively sampled from different genders and ethnicities. Interviews were conducted using a validated topic guide, and responses were audio-recorded, transcribed verbatim, checked, and analyzed using the grounded theory approach. Results A total of 30 patients were interviewed. Forty different themes and sub-themes were identified which were conceptually divided into two distinct categories related to barriers and facilitators to adherence. The barriers were: patient-specific, medication-specific, healthcare provision and system, social-cultural, and logistics. The facilitators were: having insight, perceived health benefits, regular activities, patient-provider relationship, reminders, and social support networks. Conclusions Patient-specific barriers and medication side effects were the major challenges for adhering to treatment. Perceived health benefits and having insight on the need for treatment were the most frequently cited facilitators. Targeted interventions should be developed to address the key barriers, and promote measures to facilitate adherence in this group of patients. PMID:28614368

  16. Intravenous augmentative citalopram versus clomipramine in partial/nonresponder depressed patients: a short-term, low dose, randomized, placebo-controlled study.

    PubMed

    Altamura, Alfredo Carlo; Dell'Osso, Bernardo; Buoli, Massimiliano; Zanoni, Silvia; Mundo, Emanuela

    2008-08-01

    The aim of the present study was to evaluate the efficacy of short-term low-dose intravenous augmentative citalopram (10 mg/d) versus clomipramine (25 mg/d) versus placebo in a sample of patients with MDE and partial or no response to selective serotonin reuptake inhibitors (SSRIs). Fifty-four patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, MDE and partial or no response to SSRIs per os (21-item Hamilton Depression Rating Scale [HAM-D21] score reduction, <50% or < or =25%, respectively, compared with pretreatment scores) were selected and randomized to citalopram (n = 18), clomipramine (n = 18), or placebo (n = 18) intravenous augmentation. The augmentation regimen lasted 5 days during which patients were maintained on their previous treatment with oral SSRIs. Analyses of variance with repeated measures on HAM-D(21), collected daily in blind-raters design, were performed to detect any change of depressive symptoms between the 3 groups. In addition, the number of responders and remitters was computed in the 3 groups of treatment. At end point, a significant treatment effect (F= 4.57; P = 0.015) and time-by-treatment effect (F = 11.22; P < 0.0001) were found on HAM-D21 total scores in favor of citalopram and clomipramine versus placebo, with a superiority of citalopram over clomipramine on overall symptoms (P = 0.05) as well as on anxiety-somatization symptoms (P = 0.027). The number of responders was significantly superior in the active treatment groups versus the placebo group ([chi](2)(2) = 16.36; P < 0.0001). The same result was found, considering the number of remitters ([chi](2)(2) = 13.50; P < 0.0001). Present findings suggest that both clomipramine and citalopram intravenous augmentation at low doses and for a short period are well tolerated and superior to placebo in major depressives with partial or no response to oral SSRIs with a possible superiority of citalopram over clomipramine with regard to

  17. Association between depressive symptoms, use of antidepressant medication and the metabolic syndrome: the Maine-Syracuse Study.

    PubMed

    Crichton, Georgina E; Elias, Merrill F; Robbins, Michael A

    2016-06-10

    Both depression and the metabolic syndrome (MetS) are two major public health issues. The aim of this study was to examine associations between depressive symptoms, the use of antidepressant medications, and the prevalence of MetS. Cross-sectional analyses were undertaken on 970 participants from the Maine-Syracuse Study. Depressive symptoms were measured using two self-reported depression scales, the Center for Epidemiological Studies Depression Scale (CES-D), and the Zung self-rating depression scale. Antidepressant medication use was also self-reported. MetS was defined according to the recent harmonized criteria. The risk of MetS were approximately 79 and 86 % higher for those in the highest quartile for the CESD and the Zung (CES-D: OR = 1.79, p = 0.003; Zung: OR = 1.71, p = 0.006), compared to those in the lowest quartile. With adjustment for socio-demographic variables, lifestyle factors and C-reactive protein (CRP), risk was attenuated, but remained statistically significant for the CES-D. In those who reported using antidepressant medication, the odds of having MetS were over 2-fold higher (OR = 2.22, p < 0.001, fully adjusted model), compared to those who did not use antidepressants. Both measures of depressed mood were also associated with low high density-lipoprotein (HDL) cholesterol levels. Antidepressant use was associated with elevated fasting plasma glucose concentrations, hypertension, and low HDL-cholesterol. Depressive symptoms and the use of antidepressant medications are associated with the prevalence of MetS, and with some of the individual components of the syndrome.

  18. The effects of antidepressants on human brain as detected by imaging studies. Focus on major depression.

    PubMed

    Bellani, Marcella; Dusi, Nicola; Yeh, Ping-Hong; Soares, Jair C; Brambilla, Paolo

    2011-08-15

    Recent brain imaging studies have shed light on understanding the pathogenesis of mood disorders. Evidence of structural, chemical, and functional brain changes, particularly in prefrontal cortex, cingulate, and amygdala, has been revealed in major depressive disorder (MDD). Furthermore, imaging techniques have been applied to monitor the effects of antidepressants (ADs) both in the brains of healthy volunteers and MDD patients. Although with some discrepancies due to the differences in study designs and patient samples, imaging findings have shown that ADs, particularly those having effects on the serotonergic system, modulate the volumes, functions and biochemistry of brain structures, i.e. dorsolateral prefrontal cortex, anterior cingulate and amygdala, which have been demonstrated abnormal in MDD by earlier imaging studies. This paper reviews imaging studies conducted in MDD patients and healthy controls treated with different ADs. Copyright © 2010 Elsevier Inc. All rights reserved.

  19. Increase in depression diagnoses and prescribed antidepressants among young girls. A national cohort study 2000-2013.

    PubMed

    Skovlund, Charlotte Wessel; Kessing, Lars Vedel; Mørch, Lina Steinrud; Lidegaard, Øjvind

    2017-07-01

    To analyse trends in depression diagnoses and antidepressant use according to age and gender. Nationwide cohort study including all women and men of 10-49 years living in Denmark during 2000-2013. The Psychiatric Registry and Prescription Registry provided data on depression diagnoses and antidepressant medication, respectively. Incidence rates as well as 1-year prevalence rates were calculated. The incidence and 1-year prevalence rates of depression diagnoses increased during 2000-2013. The women/men rates were 2.0 for both 1-year prevalence of depressions diagnoses and antidepressant use. For adolescent girls, the absolute increase was 3 per 1000 for depression diagnoses and 8 per 1000 for first use of antidepressants, compared to boys who had an increase of 1.1 and 3 per 1000, respectively. Before puberty, boys and girls had almost the same incidence rates of both depression diagnoses and antidepressant use throughout the period. After puberty, girls had significantly higher incidence rates than boys, and experienced during the study period a steeper increase than boys. According to age, the girls/boys incidence rate ratio of a depression diagnosis increased from 0.8 in the 10-11 year age group to 2.7 at age 12-19 years and hereafter decreased with increasing age to 1.5 at age 45-49. Depression diagnosed and first use of antidepressants increased more for girls of 12-19 years than for boys during 2000-2013, and the incidences were similar for girls and boys before puberty, but higher after puberty for girls.

  20. Factors Associated with the Combined Use of Antidepressants and Benzodiazepines in Major Depression: A Case-Control Study.

    PubMed

    Fulone, Izabela; Silva, Marcus T; Lopes, Luciane C

    2016-09-01

    The aim of this study was to identify the factors associated with the combined use of antidepressants and benzodiazepines (BDZs) in patients with major depression. We conducted a case-control study in the public health service of the city of São Paulo, Brazil. The participants were all patients being treated with antidepressants, who were diagnosed with major depression. Patients who received a combination of antidepressants and BDZs were classified as cases, and those who used only antidepressants, as controls. Data were obtained from a pharmacy database, medical records and interviews with the healthcare team. The association of predisposing factors for combined therapy was analysed using logistic regression analysis, and the odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Of the 1355 users of antidepressants, 265 had major depression, of whom 138 were cases and 127 were controls. The factors associated with combined use were age older than 35 years (OR 2.2, 95% CI 1.0-4.7), absence of comorbidities (OR 2.3, 95% CI 1.4-4.1) and no use of other drugs (OR 1.9, 95% CI 1.1-3.3). Patients with combined use were more likely to exhibit inadequate prescribing, including inappropriate antidepressants (OR 4.7, 95% CI 2.2-9.9), inadequate dosages (OR 3.62, 95% CI 1.4-9.6) and/or a non-recommended duration (OR 66.6, 95% CI 18.4-240.7). The factors identified showed the groups most susceptible to combined use in this population, who in turn are more likely to receive inappropriate prescriptions.

  1. Childhood Predictors of Use and Costs of Antidepressant Medication by Age 24 Years: Findings from the Finnish Nationwide 1981 Birth Cohort Study

    ERIC Educational Resources Information Center

    Gyllenberg, David; Sourander, Andre; Niemela, Solja; Helenius, Hans; Sillanmaki, Lauri; Ristkari, Terja; Piha, Jorma; Kumpulainen, Kirsti; Tamminen, Tuula; Moilanen, Irma; Almqvist, Fredrik

    2011-01-01

    Objective: Prior studies on antidepressant use in late adolescence and young adulthood have been cross-sectional, and prospective associations with childhood psychiatric problems have not been examined. The objective was to study the association between childhood problems and lifetime prevalence and costs of antidepressant medication by age 24…

  2. Childhood Predictors of Use and Costs of Antidepressant Medication by Age 24 Years: Findings from the Finnish Nationwide 1981 Birth Cohort Study

    ERIC Educational Resources Information Center

    Gyllenberg, David; Sourander, Andre; Niemela, Solja; Helenius, Hans; Sillanmaki, Lauri; Ristkari, Terja; Piha, Jorma; Kumpulainen, Kirsti; Tamminen, Tuula; Moilanen, Irma; Almqvist, Fredrik

    2011-01-01

    Objective: Prior studies on antidepressant use in late adolescence and young adulthood have been cross-sectional, and prospective associations with childhood psychiatric problems have not been examined. The objective was to study the association between childhood problems and lifetime prevalence and costs of antidepressant medication by age 24…

  3. Two Phase III randomised double-blind studies of fixed-dose TC-5214 (dexmecamylamine) adjunct to ongoing antidepressant therapy in patients with major depressive disorder and an inadequate response to prior antidepressant therapy.

    PubMed

    Möller, Hans-Jürgen; Demyttenaere, Koen; Olausson, Bengt; Szamosi, Johan; Wilson, Ellis; Hosford, David; Dunbar, Geoffrey; Tummala, Raj; Eriksson, Hans

    2015-10-01

    To evaluate the neuronal nicotinic channel modulator TC-5214 (dexmecamylamine) as adjunct therapy in patients with major depressive disorder (MDD) and inadequate response to prior antidepressant treatment. Study 004 (D4130C00004) and Study 005 (D4130C00005) comprised an 8-week open-label antidepressant (SSRI/SNRI) treatment period followed by an 8-week randomised, active treatment with twice-daily TC-5214 (0.5, 2 or 4 mg in Study 004; 0.1, 1 or 4 mg in Study 005) or placebo, adjunct to ongoing SSRI/SNRI. Primary efficacy endpoint was change in MADRS total score from randomisation (Week 8) to treatment end (Week 16). Secondary endpoints included MADRS response and remission, and changes in SDS and HAM-D-17-item scores. Safety and tolerability were monitored throughout. Studies 004 and 005 randomised 640 and 696 patients, respectively, to TC-5214 or placebo. No statistically significant improvements in MADRS total score or any secondary endpoints were seen with TC-5214 versus placebo in either study at treatment end. The most commonly reported adverse events (> 10%) with TC-5214 were constipation, dizziness and dry mouth. TC-5214 adjunct to antidepressant was generally well tolerated. However, the studies were not supportive of an antidepressant effect for TC-5214 in patients with MDD and inadequate response to prior antidepressant therapy.

  4. Nonresponders to pharyngeal surgery for obstructive sleep apnea: insights from drug-induced sleep endoscopy.

    PubMed

    Kezirian, Eric J

    2011-06-01

    To examine drug-induced sleep endoscopy (DISE) findings in nonresponders to previous pharyngeal obstructive sleep apnea (OSA) surgery. Cross-sectional. DISE using propofol for unconscious sedation was performed in nonresponders to previous OSA surgery (including palate surgery with or without tonsillectomy and possible other procedures). Nonresponders were defined as subjects with a postoperative apnea-hypopnea index more than 10 events/hr. Recorded findings from DISE included the presence and degree of obstruction in the palatal and hypopharyngeal regions, the contributions of specific structures (velum, oropharyngeal lateral walls, tongue, and/or epiglottis) to upper airway obstruction, and the degree of mouth opening. Thirty-three nonresponders underwent DISE examinations. Age was 46.2 ± 11.8 years, and 9% (3 of 33) were female. On diagnostic sleep studies prior to DISE, the apnea-hypopnea index was 43.4 ± 26.6 events/hr. During DISE, a majority of subjects demonstrated residual palatal obstruction, and almost all demonstrated hypopharyngeal obstruction. A diversity of individual structures contributed to upper airway obstruction, often in combination. Moderate to severe mouth opening occurred in one-third of subjects and was associated with narrowing of upper airway dimensions. Residual upper airway obstruction in surgery nonresponders likely occurs due to multiple mechanisms, and DISE may enhance the understanding of them. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

  5. Which antidepressant?

    PubMed Central

    Matthews, K; Eagles, J M

    1991-01-01

    The prescription of psychotropic drugs, and particularly the use of antidepressants, has received considerable attention in the medical literature, the media and from legislative bodies in recent years. Medical practitioners are faced with a bewildering array of apparently efficacious drugs from which they must choose when prescribing for a depressed patient. This paper discusses the main parameters which guide this choice, namely clinical efficacy, adverse effects profile, safety in overdose and monetary cost. It concludes by making some recommendations for the prescription of antidepressant drugs. PMID:2031757

  6. A comparison of responders and nonresponders to oral appliance therapy for the treatment of obstructive sleep apnea.

    PubMed

    Otsuka, Ryo; Almeida, Fernanda Ribeiro de; Lowe, Alan A; Ryan, Frank

    2006-02-01

    This retrospective study compared cephalometric variables between responders and nonresponders to a titratable oral appliance (OA) in a group of subjects matched for sex, pretreatment age, and body mass index (BMI). Nine nonresponders as defined by an improvement in the apnea hypopnea index (AHI; <20%) and their individually matched responders were selected for this study. The difference in age for each matched pair was +/-5 years, and, for BMI, the difference was +/-15%. The pretreatment AHI was matched to the same category (moderate, >15 to < or =30; severe I, >30 to < or =45; and severe II, >45 AHI). Middle and inferior airway space and oropharyngeal airway cross-sectional area were significantly larger in the nonresponders. Position of the mandible relative to the cervical spine was the only significant skeletal variable and was larger in nonresponders. Changes in BMI between the groups were statistically significant; the averages were a 2.9% increase in the nonresponders and a 0.5% decrease in responders. The wider airway in nonresponders might reflect an enhanced neuromuscular compensation while awake. The weight gain in nonresponders was relatively small, but it might have reduced the effectiveness of the OA. When treating OSA patients with OA therapy, clinicians should pay particular attention to airway size and weight changes.

  7. Antidepressants and Valvular Heart Disease

    PubMed Central

    Lin, Chia-Hui; Hsiao, Fei-Yuan; Liu, Yen-Bin; Gau, Susan Shur-Fen; Wang, Chi-Chuan; Shen, Li-Jiuan

    2016-01-01

    Abstract Empirical evidence regarding the association between antidepressants and valvular heart disease (VHD) is scarce. Using Taiwan's National Health Insurance Research database, this nested case-control study assessed the association between antidepressants and VHD in a Chinese population. Among a cohort of patients who used at least 3 prescription antidepressants, 874 cases with VHD and 3496 matched controls (1:4 ratio) were identified. Conditional logistic regression models were used to examine the timing, duration, dose and type of antidepressants use, and the risk of VHD. Current use of antidepressants was associated with a 1.4-fold increase in the risk of VHD (adjusted odds ratio [aOR] 1.44; 95% confidence interval [CI] 1.17–1.77). Among current users, a dose–response association was observed in terms of the cumulative duration and the cumulative antidepressant dose. Significantly higher risks of VHD were observed among the current users of tricyclic antidepressants (aOR 1.40 [1.05–1.87]). We found that the use of antidepressants was associated with a greater risk of VHD and that the risks varied according to different antidepressants. PMID:27057841

  8. Antidepressants with a high serotonin reuptake transporter affinity and serum lipid levels in a population-based study in older adults.

    PubMed

    Noordam, Raymond; Aarts, Nikkie; de Keyser, Catherine E; Hofman, Albert; Stricker, Bruno H; Visser, Loes E

    2015-10-01

    We aimed to investigate the association between antidepressants and serum lipid levels in a population-based study in older adults. We included participants from the prospective Rotterdam Study with data on lipid levels (total, low-density lipoprotein (LDL) and high-density lipoprotein cholesterol, and triglycerides). We classified antidepressants based on binding affinity to the serotonin transporter (low/intermediate- and high-affinity antidepressants). We compared lipid levels in users of these groups of antidepressants with lipid levels in non-users. Furthermore, we studied effect modification by the 102 C>T polymorphism (HTR2A gene), which is associated with antidepressant drug response and metabolic outcomes. Compared with non-users (N = 6438), LDL cholesterol level was higher (2.9 versus 3.1 mmol/L, respectively; p = 0.05) in users of high-affinity antidepressants (N = 89). Similar levels of the other lipids were observed between the groups for the other lipids. The mean difference in serum LDL cholesterol level between non-users and users of high-affinity antidepressants was largest in participants with the CC genotype compared with the other genotypes (notably 0.47 mmol/L), indicative of effect modification (p-value for interaction = 0.03). Antidepressants with a high serotonin reuptake transporter affinity were associated with higher LDL cholesterol levels, which were modified by a common genetic variation in the HTR2A gene. © The Author(s) 2015.

  9. Antidepressants During Pregnancy Safe for Baby

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_166353.html Antidepressants During Pregnancy Safe for Baby: Study It finds ... News) -- Expectant mothers, if you're taking an antidepressant it won't make your newborn cranky or ...

  10. NCI-funded CCOP Study Shows Antidepressant Drug Relieves Painful Neuropathy from Chemotherapy | Division of Cancer Prevention

    Cancer.gov

    The antidepressant drug duloxetine, known commercially as Cymbalta, helped relieve painful numbness and tingling feelings caused by chemotherapy in 59 percent of patients, a new study finds. This is the first clinical trial to find an effective treatment for this pain. Chemotherapy-induced peripheral neuropathy is a common side effect of certain chemotherapy drugs. |

  11. Augmenting Antidepressant Medication Treatment of Depressed Women with Emotionally Focused Therapy for Couples: A Randomized Pilot Study

    ERIC Educational Resources Information Center

    Denton, Wayne H.; Wittenborn, Andrea K.; Golden, Robert N.

    2012-01-01

    This is the first study to evaluate adding emotionally focused therapy for couples (EFT) to antidepressant medication in the treatment of women with major depressive disorder and comorbid relationship discord. Twenty-four women and their male partners were randomized to 6 months of medication management alone (MM) or MM augmented with EFT (MM +…

  12. Augmenting Antidepressant Medication Treatment of Depressed Women with Emotionally Focused Therapy for Couples: A Randomized Pilot Study

    ERIC Educational Resources Information Center

    Denton, Wayne H.; Wittenborn, Andrea K.; Golden, Robert N.

    2012-01-01

    This is the first study to evaluate adding emotionally focused therapy for couples (EFT) to antidepressant medication in the treatment of women with major depressive disorder and comorbid relationship discord. Twenty-four women and their male partners were randomized to 6 months of medication management alone (MM) or MM augmented with EFT (MM +…

  13. Generalizing from clinical trial data: A case study. The risk of suicidality among pediatric antidepressant users

    PubMed Central

    Greenhouse, Joel B.; Kaizar, Eloise E.; Kelleher, Kelly; Seltman, Howard; Gardner, William

    2010-01-01

    Summary For the results of randomized controlled clinical trials (RCTs) and related meta-analyses to be useful in practice, they must be relevant to a definable group of patients in a particular clinical setting. To the extent this is so, we say that the trial is generalizable or externally valid. Although concern about the generalizability of the results of RCTs is often discussed, there are few examples of methods for assessing the generalizability of clinical trial data. In this paper, we describe and illustrate an approach for making what we call generalizability judgments and illustrate the approach in the context of a case study of the risk of suicidality among pediatric antidepressant users. PMID:18381709

  14. Breastfeeding and Antidepressants

    PubMed Central

    Field, Tiffany

    2008-01-01

    Although a large literature supports the benefits of breastfeeding, this review suggests that breastfeeding is less common among postpartum depressed women, even though their infants benefit from the breastfeeding. Depressed mothers, in part, do not breastfeed because of their concern about potentially negative effects of antidepressants on their infants. Although sertraline (Zoloft) and paroxetine (Paxol) concentrations are not detectable in infants’ sera, fluoxetine (Prozac) and citalopram (Celexa) do have detectable levels. Unfortunately these findings are not definitive because they are based on very small sample, uncontrolled studies. As in the literature on prenatal antidepressant effects, the question still remains whether the antidepressants or the untreated depression itself has more negative effects on the infant. It is possible that the positive effects of breastfeeding may outweigh the positive effects of the antidepressants for both the mother and the infant. In addition, some alternative therapies may substitute or attenuate the effects of antidepressants, such as vagal stimulation or massage therapy, both therapies being noted to reduce depression. Further studies of this kind are needed to determine the optimal course of therapy for the benefit of the depressed, breastfeeding mother and the breastfed infant. PMID:18272227

  15. Breastfeeding and antidepressants.

    PubMed

    Field, Tiffany

    2008-09-01

    Although a large literature supports the benefits of breastfeeding, this review suggests that breastfeeding is less common among postpartum depressed women, even though their infants benefit from the breastfeeding. Depressed mothers, in part, do not breastfeed because of their concern about potentially negative effects of antidepressants on their infants. Although sertraline (Zoloft) and paroxetine (Paxol) concentrations are not detectable in infants' sera, fluoxetine (Prozac) and citalopram (Celexa) do have detectable levels. Unfortunately these findings are not definitive because they are based on very small sample, uncontrolled studies. As in the literature on prenatal antidepressant effects, the question still remains whether the antidepressants or the untreated depression itself has more negative effects on the infant. It is possible that the positive effects of breastfeeding may outweigh the positive effects of the antidepressants for both the mother and the infant. In addition, some alternative therapies may substitute or attenuate the effects of antidepressants, such as vagal stimulation or massage therapy, both therapies being noted to reduce depression. Further studies of this kind are needed to determine the optimal course of therapy for the benefit of the depressed, breastfeeding mother and the breastfed infant.

  16. Antidepressant Utilization and Suicide in Europe: An Ecological Multi-National Study

    PubMed Central

    Gusmão, Ricardo; Quintão, Sónia; McDaid, David; Arensman, Ella; Van Audenhove, Chantal; Coffey, Claire; Värnik, Airi; Värnik, Peeter; Coyne, James; Hegerl, Ulrich

    2013-01-01

    Background Research concerning the association between use of antidepressants and incidence of suicide has yielded inconsistent results and is the subject of considerable controversy. The first aim is to describe trends in the use of antidepressants and rates of suicide in Europe, adjusted for gross domestic product, alcohol consumption, unemployment, and divorce. The second aim is to explore if any observed reduction in the rate of suicide in different European countries preceded the trend for increased use of antidepressants. Methods Data were obtained for 29 European countries between 1980 and 2009. Pearson correlations were used to explore the direction and magnitude of associations. Generalized linear mixed models and Poisson regression distribution were used to clarify the effects of antidepressants on suicide rates, while an autoregressive adjusted model was used to test the interaction between antidepressant utilization and suicide over two time periods: 1980–1994 and 1995–2009. Findings An inverse correlation was observed in all countries between recorded Standardised Death Rate (SDR) for suicide and antidepressant Defined Daily Dosage (DDD), with the exception of Portugal. Variability was marked in the association between suicide and alcohol, unemployment and divorce, with countries depicting either a positive or a negative correlation with the SDR for suicide. Every unit increase in DDD of an antidepressant per 1000 people per day, adjusted for these confounding factors, reduces the SDR by 0.088. The correlation between DDD and suicide related SDR was negative in both time periods considered, albeit more pronounced between 1980 and 1994. Conclusions Suicide rates have tended to decrease more in European countries where there has been a greater increase in the use of antidepressants. These findings underline the importance of the appropriate use of antidepressants as part of routine care for people diagnosed with depression, therefore reducing the

  17. Neuronal and immunological basis of action of antidepressants in chronic pain - clinical and experimental studies.

    PubMed

    Mika, Joanna; Zychowska, Magdalena; Makuch, Wioletta; Rojewska, Ewelina; Przewlocka, Barbara

    2013-01-01

    The current knowledge of the pharmacological actions of the tricyclic antidepressants (TCAs) has slowly evolved through their over 40-year history. Chronic pain represents one of the most important public health problems, and antidepressants are an essential part of the therapeutic strategy in addition to classical analgesics. This article reviews the available evidence on the efficacy and safety of antidepressants in chronic pain conditions; namely, headaches, low back pain, fibromyalgia, cancer pain and especially neuropathic pain. TCAs are traditionally the main type of depression medication used to treat chronic pain. Recently, new antidepressants were introduced into clinical use, with a significant reduction in side effects and equivalent efficacy on mood disorders. These new drugs that are effective for chronic pain belong to the tetracyclic antidepressants (TeCAs) group (amoxapine, maprotiline), the serotonin and noradrenaline reuptake inhibitors (SNRIs) group (duloxetine, venlafaxine, milnacipran) and the atypical antidepressants group (bupropion, trazodone, mirtazapine, nefazodone). In this review, we present the available publications on TCAs (amitriptyline, doxepin, imipramine, desipramine, nortriptyline), TeCAs (amoxapine, maprotiline), selective serotonin reuptake inhibitors (SSRIs) (citalopram, fluoxetine, paroxetine), SNRIs (duloxetine, venlafaxine, milnacipran) and atypical antidepressants (bupropion) for the treatment of neuropathic pain. We also review analgesics acting as both opioid receptor agonists and also acting as aminergic reuptake inhibitors. Existing data are insufficient to conclude which of these new classes of antidepressants has the best clinical profile and will be the most effective in the treatment of neuropathic pain; in addition, a lower incidence of side effects should be considered. Increased experimental and translational research is a key for further improvement of the treatment of chronic pain with antidepressants. However

  18. Telephone counseling as an adjunct to antidepressant treatment in the primary care system. A pilot study.

    PubMed

    Tutty, S; Simon, G; Ludman, E

    2000-01-01

    Many clinical and logistical barriers exist in the primary care model for treating adult depression. To examine the feasibility and clinical effects of a telephone counseling and medication monitoring program for adults starting treatment for depression in primary care. Pilot study with a contemporaneous control group. Group Health Cooperative, an HMO serving more than 450,000 persons in western Washington. Twenty-eight adult primary care patients starting antidepressant treatment (telephone counseling group) were compared with 94 patients receiving usual care (control group). Telephone counseling participants received written educational materials addressing depression, followed by six weekly counseling and support sessions delivered over the telephone by a master's-level therapist. The intervention used the transtheoretical model of behavioral change and cognitive-behavioral strategies to enhance self-monitoring, self-management, and coping skills. Telephone interviews and computerized pharmacy and visit records. Participation rate and retention, Hopkins symptom checklist depression scores, medication adherence and dose thresholds, and visits made for depression treatment. Ninety-three percent of telephone counseling participants contacted agreed to participate, and 92% completed the intervention. Telephone counseling patients showed significantly lower depressive symptoms than did control group patients at 3-month follow-up (0.89 vs. 1.13) and 6-month follow-up (0.79 vs. 0.95; P = 0.03). Telephone counseling patients were twice as likely to adhere to antidepressant medication with adequate dose thresholds (25% vs. 13%) and half as likely to meet criteria for major depression than were control group patients across time (8% vs. 16%), although these differences were not statistically significant. Total outpatient visits made for depression treatment between groups across time did not differ. Overall program cost per patient was estimated at about $150. A telephone

  19. Neurodevelopment of children prenatally exposed to selective reuptake inhibitor antidepressants: Toronto sibling study.

    PubMed

    Nulman, Irena; Koren, Gideon; Rovet, Joanne; Barrera, Maru; Streiner, David L; Feldman, Brian M

    2015-07-01

    The reproductive safety of selective reuptake inhibitor (SRI) antidepressants needs to be established to provide optimal control of maternal depression while protecting the fetus. To define a child's neurodevelopment following prenatal exposure to SRIs and to account for genetic and environmental confounders in a sibling design using the Toronto Motherisk prospective database. Intelligence and behavior of siblings prenatally exposed and unexposed to SRIs were assessed by using the Wechsler Preschool and Primary Scale of Intelligence-Third Edition, Child Behavior Checklist, and Conners Parent Rating Scale-Revised and subsequently compared. Mothers, diagnosed with depression using DSM-IV, were assessed for intelligence quotient (IQ) and for severity of depressive symptoms with the Center for Epidemiologic Studies Depression scale. Prenatal drug doses and durations of exposure, child's age, child's sex, birth order, severity of maternal depression symptoms, and Full Scale IQ, the primary outcome measure, of both the mother and the child were considered in the analyses. Forty-five sibling pairs (ages 3 years to 6 years 11 months, prenatally exposed and unexposed to SRIs) did not differ in their mean ± SD Full Scale IQs (103 ± 13 vs 106 ± 12; P = .30; 95% CI, -7.06 to 2.21) or rates of problematic behaviors. Significant predictor of children's intelligence was maternal IQ (P = .043, β = 0.306). Severity of maternal depression was a significant predictor of Child Behavior Checklist Internalizing (P = .019, β = 0.366), Externalizing (P = .003, β = 0.457), and Total scores (P = .001, β = 0.494). Drug doses and durations of exposure during pregnancy did not predict any outcomes of interest in the exposed siblings. SRI antidepressants were not found to be neurotoxic. Maternal depression may risk the child's future psychopathology. The sibling design in behavioral teratology aids in separating the effects of maternal depression from those of SRIs, providing stronger

  20. International study on antidepressant prescription pattern at 20 teaching hospitals and major psychiatric institutions in East Asia: Analysis of 1898 cases from China, Japan, Korea, Singapore and Taiwan.

    PubMed

    Uchida, Naoki; Chong, Mian-Yoon; Tan, Chay Hoon; Nagai, Hiroshi; Tanaka, Mariko; Lee, Min-Soo; Fujii, Senta; Yang, Shu-Yu; Si, Tainmei; Sim, Kang; Wei, Hao; Ling, He Yan; Nishimura, Ryoji; Kawaguchi, Yoshichika; Edwards, Glen; Sartorius, Norman; Shinfuku, Naotaka

    2007-10-01

    The purpose of the present study was to review the prescription patterns of antidepressants in different countries in East Asia. The survey was conducted in China, Japan, Korea, Singapore and Taiwan from October 2003 to March 2004 using the unified research protocol and questionnaire. Twenty teaching hospitals and major psychiatric hospitals participated and a total of 1898 patients receiving antidepressants were analyzed. The survey provided a number of interesting characteristics on the prescription patterns of antidepressant in East Asia. Out of 56 antidepressants listed in the Anatomical Therapeutic Chemical Classification (ATC) index by the World Health Organization (WHO) Collaborating Center for Drug Statistics Methodology (Oslo), only 26 antidepressants were prescribed in participating countries in East Asia. On average 38.4% of prescriptions of antidepressants were for patients with diagnoses other than depressive disorders. The availability and commonly prescribed antidepressants varied greatly by country. The selective serotonin re-uptake inhibitors (SSRI) and other newer antidepressants were prescribed in approximately 77.0% of all cases. At the time of the survey, only two SSRI medications were available in Japan. However, five types of SSRI were available and were often prescribed in Korea.

  1. Is there any evidence to support the use of anti-depressants in painful rheumatological conditions? Systematic review of pharmacological and clinical studies.

    PubMed

    Perrot, S; Javier, R-M; Marty, M; Le Jeunne, C; Laroche, F

    2008-08-01

    The aim of this study was to review the evidence supporting the use of anti-depressants in painful rheumatological conditions. A systematic review of papers published between 1966 and 2007, in five European languages, on anti-depressants in rheumatological conditions was performed. Papers were scored using Jadad method and analgesic ES was calculated. We selected 78 clinical studies and 12 meta-analyses, from 140 papers. The strongest evidence of an analgesic effect of anti-depressants has been obtained for fibromyalgia. A weak analgesic effect is observed for chronic low back pain, with an efficacy level close to that of analgesics. In RA and AS, there is no analgesic effect of anti-depressants, but these drugs may help to manage fatigue and sleep disorders. There is no clear evidence of an analgesic effect inOA, but studies have poor methodological quality. Analgesic effects of anti-depressants are independent of their anti-depressant effects. Tricyclic anti-depressants (TCAs), even at low doses, have analgesic effects equivalent to those of serotonin and noradrenalin reuptake inhibitors (SNRIs), but are less well tolerated. Selective serotonin reuptake inhibitors (SSRIs) have modest analgesic effects, but higher doses are required to achieve analgesia. Anti-depressant drugs, particularly TCAs and SNRIs, have analgesic effects in chronic rheumatic painful states in which analgesics and NSAIDs are not very efficient, such as fibromyalgia and chronic low back pain. In inflammatory rheumatic diseases, anti-depressants may be useful for managing fatigue and sleep disorders. Further studies are required to compare anti-depressants with other analgesics in the management of chronic painful rheumatological conditions.

  2. Establishing moderators and biosignatures of antidepressant response in clinical care (EMBARC): Rationale and design.

    PubMed

    Trivedi, Madhukar H; McGrath, Patrick J; Fava, Maurizio; Parsey, Ramin V; Kurian, Benji T; Phillips, Mary L; Oquendo, Maria A; Bruder, Gerard; Pizzagalli, Diego; Toups, Marisa; Cooper, Crystal; Adams, Phil; Weyandt, Sarah; Morris, David W; Grannemann, Bruce D; Ogden, R Todd; Buckner, Randy; McInnis, Melvin; Kraemer, Helena C; Petkova, Eva; Carmody, Thomas J; Weissman, Myrna M

    2016-07-01

    Remission rates for Major Depressive Disorder (MDD) are low and unpredictable for any given antidepressant. No biological or clinical marker has demonstrated sufficient ability to match individuals to efficacious treatment. Biosignatures developed from the systematic exploration of multiple biological markers, which optimize treatment selection for individuals (moderators) and provide early indication of ultimate treatment response (mediators) are needed. The rationale and design of a multi-site, placebo-controlled randomized clinical trial of sertraline examining moderators and mediators of treatment response is described. The target sample is 300 participants with early onset (≤30 years) recurrent MDD. Non-responders to an 8-week trial are switched double blind to either bupropion (for sertraline non-responders) or sertraline (for placebo non-responders) for an additional 8 weeks. Clinical moderators include anxious depression, early trauma, gender, melancholic and atypical depression, anger attacks, Axis II disorder, hypersomnia/fatigue, and chronicity of depression. Biological moderator and mediators include cerebral cortical thickness, task-based fMRI (reward and emotion conflict), resting connectivity, diffusion tensor imaging (DTI), arterial spin labeling (ASL), electroencephalograpy (EEG), cortical evoked potentials, and behavioral/cognitive tasks evaluated at baseline and week 1, except DTI, assessed only at baseline. The study is designed to standardize assessment of biomarkers across multiple sites as well as institute replicable quality control methods, and to use advanced data analytic methods to integrate these markers. A Differential Depression Treatment Response Index (DTRI) will be developed. The data, including biological samples (DNA, RNA, and plasma collected before and during treatment), will become available in a public scientific repository. Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for

  3. Pregabalin augmentation of antidepressants in older patients with comorbid depression and generalized anxiety disorder-an open-label study.

    PubMed

    Karaiskos, Dimitrios; Pappa, Dimitra; Tzavellas, Elias; Siarkos, Kostas; Katirtzoglou, Everina; Papadimitriou, George N; Politis, Antonios

    2013-01-01

    The objective of this 12-week open-label study was to evaluate the efficacy, safety, and tolerability of pregabalin as an adjunctive treatment to antidepressants in older patients suffering from depression and comorbid generalized anxiety disorder (GAD). The initial sample of this open-label study consisted of 94 older patients fulfilling criteria for depression with comorbid GAD who were treated with antidepressants. Twenty of them who had received antidepressant monotherapy for an adequate time and shown partial response to the antidepressant prescribed, in terms of either anxiety or depressive symptomatology, followed the next phase. During the 12-week study period, pregabalin was gradually added to the previously prescribed antidepressant, reaching 225 mg/day over 4 weeks. Depression and anxiety scores as well as side effects were monitored. Within groups, differences of depression and anxiety scores at baseline and during the following 12 weeks of treatment were estimated with repeated-measure analysis of variance. A statistical significant reduction in depression scores was observed after the 4th week of treatment (p < 0.01), which further improved between the 8th and 12th weeks (p < 0.01). Concerning overall anxiety scores, a statistically significant improvement was noted between the 2nd and 4th weeks (p < 0.01), which further continued throughout the 8th (p < 0.05) and 12th weeks (p < 0.05). The present study demonstrated a good therapeutic response to pregabalin in patients with depression comorbid with GAD after a 12-week treatment period. Both anxiety and depressive symptomatology significantly improved, and minimal side effects were observed. Copyright © 2012 John Wiley & Sons, Ltd.

  4. Antidepressants and antipsychotics classified with torsades de pointes arrhythmia risk and mortality in older adults ‐ a Swedish nationwide study

    PubMed Central

    Collin, Julius; Jonasdottir Bergman, Gudrun; Borg, Natalia; Salmi, Peter; Fastbom, Johan

    2016-01-01

    Aim The aim of the study was to examine mortality risk associated with use of antidepressants and antipsychotics classified with torsades de pointes (TdP) risk in elderly. Methods A matched case–control register study was conducted in people 65 years and older dying outside hospital from 2008–2013 (n = 286 092) and matched controls (n = 1 430 460). The association between prescription of antidepressants and antipsychotics with various TdP risk according to CredibleMeds (www.crediblemeds.org) and all‐cause mortality was studied by multivariate conditional logistic regression adjusted for comorbidity and several other confounders. Results Use of antidepressants classified with known or possible TdP risk, was associated with higher adjusted risk for mortality (OR 1.53, 95% CI 1.51, 1.56 and OR 1.63, 95% CI 1.61, 1.67, respectively) compared with antidepressants classified with conditional TdP risk (OR 1.25, 95% CI 1.22, 1.28) or without TdP classification (OR 0.99, 95% CI 0.94, 1.05). Antipsychotics classified with known TdP risk were associated with higher risk (OR 4.57, 95% CI 4.37, 4.78) than antipsychotics with possible risk (OR 2.58, 95% CI 2.52, 2.64) or without TdP classification (OR 2.14, 95% CI 2.03, 2.65). The following risk ranking was observed for commonly used antidepressants: mirtazapine > citalopram > sertraline > amitriptyline and for antipsychotics: haloperidol > risperidone >olanzapine > quetiapine. Conclusion The CredibleMeds system predicted drug‐associated risk for mortality in the elderly at the risk class level. Among antipsychotics, haloperidol, and among antidepressants, mirtazapine and citalopram, were associated with the highest risks. The results suggest that the TdP risk with antidepressants and antipsychotics should be taken into consideration when prescribing to the elderly. PMID:26574175

  5. Antidepressants and antipsychotics classified with torsades de pointes arrhythmia risk and mortality in older adults - a Swedish nationwide study.

    PubMed

    Danielsson, Bengt; Collin, Julius; Jonasdottir Bergman, Gudrun; Borg, Natalia; Salmi, Peter; Fastbom, Johan

    2016-04-01

    The aim of the study was to examine mortality risk associated with use of antidepressants and antipsychotics classified with torsades de pointes (TdP) risk in elderly. A matched case-control register study was conducted in people 65 years and older dying outside hospital from 2008-2013 (n = 286,092) and matched controls (n = 1,430,460). The association between prescription of antidepressants and antipsychotics with various TdP risk according to CredibleMeds (www.crediblemeds.org) and all-cause mortality was studied by multivariate conditional logistic regression adjusted for comorbidity and several other confounders. Use of antidepressants classified with known or possible TdP risk, was associated with higher adjusted risk for mortality (OR 1.53, 95% CI 1.51, 1.56 and OR 1.63, 95% CI 1.61, 1.67, respectively) compared with antidepressants classified with conditional TdP risk (OR 1.25, 95% CI 1.22, 1.28) or without TdP classification (OR 0.99, 95% CI 0.94, 1.05). Antipsychotics classified with known TdP risk were associated with higher risk (OR 4.57, 95% CI 4.37, 4.78) than antipsychotics with possible risk (OR 2.58, 95% CI 2.52, 2.64) or without TdP classification (OR 2.14, 95% CI 2.03, 2.65). The following risk ranking was observed for commonly used antidepressants: mirtazapine > citalopram > sertraline > amitriptyline and for antipsychotics: haloperidol > risperidone >olanzapine > quetiapine. The CredibleMeds system predicted drug-associated risk for mortality in the elderly at the risk class level. Among antipsychotics, haloperidol, and among antidepressants, mirtazapine and citalopram, were associated with the highest risks. The results suggest that the TdP risk with antidepressants and antipsychotics should be taken into consideration when prescribing to the elderly. © 2015 The British Pharmacological Society.

  6. Evaluation of antidepressant like activity of curcumin and its combination with fluoxetine and imipramine: an acute and chronic study.

    PubMed

    Sanmukhani, Jayesh; Anovadiya, Ashish; Tripathi, Chandrabhanu B

    2011-01-01

    Curcumin is the active ingredient of commonly used spice Curuma longa Linn. In the present study, the antidepressant like activity of curcumin and its combination with fluoxetine and imipramine was studied in acute model (three doses 24, 5 and 1 h before test) of forced swimming test (FST) in glass jar and tail suspension test (TST) in mice and in chronic model (14 day study) of FST with water wheel in rats. All the tests were carried out in the following seven groups (n = 6 in each group), drugs being given orally (doses for mice): Group 1 (vehicle), group 2 (curcumin 50 mg/kg), group 3 (curcumin 100 mg/kg), group 4 (fluoxetine 20 mg/kg), group 5 (imipramine 15 mg/kg), group 6 (curcumin 100 mg/kg plus fluoxetine 20 mg/kg) and group 7 (curcumin 100 mg/kg plus imipramine 15 mg/kg). Equivalent doses for rats were used. Both the acute model of FST and TST, and the chronic model of FST with water wheel showed significant antidepressant like activity of curcumin in 100 mg/kg dose as compared to vehicle control (p < 0.05). The effect of curcumin (100 mg/kg) was similar to that of fluoxetine and imipramine (p > 0.05) but its addition to fluoxetine and imipramine did not improve their antidepressant activity (p > 0.05). Curcumin increased both the swimming and climbing behavior in FST, thus its antidepressant like activity could be due to an increase in serotonin, norepinephrine and dopamine levels in the brain. Curcumin can be a useful antidepressant especially in cases which respond to drugs having mixed effects on serotonin and catecholamines levels in the brain.

  7. Changes in antidepressant use by young people and suicidal behavior after FDA warnings and media coverage: quasi-experimental study.

    PubMed

    Lu, Christine Y; Zhang, Fang; Lakoma, Matthew D; Madden, Jeanne M; Rusinak, Donna; Penfold, Robert B; Simon, Gregory; Ahmedani, Brian K; Clarke, Gregory; Hunkeler, Enid M; Waitzfelder, Beth; Owen-Smith, Ashli; Raebel, Marsha A; Rossom, Rebecca; Coleman, Karen J; Copeland, Laurel A; Soumerai, Stephen B

    2014-06-18

    To investigate if the widely publicized warnings in 2003 from the US Food and Drug Administration about a possible increased risk of suicidality with antidepressant use in young people were associated with changes in antidepressant use, suicide attempts, and completed suicides among young people. Quasi-experimental study assessing changes in outcomes after the warnings, controlling for pre-existing trends. Automated healthcare claims data (2000-10) derived from the virtual data warehouse of 11 health plans in the US Mental Health Research Network. Study cohorts included adolescents (around 1.1 million), young adults (around 1.4 million), and adults (around 5 million). Rates of antidepressant dispensings, psychotropic drug poisonings (a validated proxy for suicide attempts), and completed suicides. Trends in antidepressant use and poisonings changed abruptly after the warnings. In the second year after the warnings, relative changes in antidepressant use were -31.0% (95% confidence interval -33.0% to -29.0%) among adolescents, -24.3% (-25.4% to -23.2%) among young adults, and -14.5% (-16.0% to -12.9%) among adults. These reflected absolute reductions of 696, 1216, and 1621 dispensings per 100,000 people among adolescents, young adults, and adults, respectively. Simultaneously, there were significant, relative increases in psychotropic drug poisonings in adolescents (21.7%, 95% confidence interval 4.9% to 38.5%) and young adults (33.7%, 26.9% to 40.4%) but not among adults (5.2%, -6.5% to 16.9%). These reflected absolute increases of 2 and 4 poisonings per 100,000 people among adolescents and young adults, respectively (approximately 77 additional poisonings in our cohort of 2.5 million young people). Completed suicides did not change for any age group. Safety warnings about antidepressants and widespread media coverage decreased antidepressant use, and there were simultaneous increases in suicide attempts among young people. It is essential to monitor and reduce

  8. Changes in antidepressant use by young people and suicidal behavior after FDA warnings and media coverage: quasi-experimental study

    PubMed Central

    Zhang, Fang; Lakoma, Matthew D; Madden, Jeanne M; Rusinak, Donna; Penfold, Robert B; Simon, Gregory; Ahmedani, Brian K; Clarke, Gregory; Hunkeler, Enid M; Waitzfelder, Beth; Owen-Smith, Ashli; Raebel, Marsha A; Rossom, Rebecca; Coleman, Karen J; Copeland, Laurel A; Soumerai, Stephen B

    2014-01-01

    Objective To investigate if the widely publicized warnings in 2003 from the US Food and Drug Administration about a possible increased risk of suicidality with antidepressant use in young people were associated with changes in antidepressant use, suicide attempts, and completed suicides among young people. Design Quasi-experimental study assessing changes in outcomes after the warnings, controlling for pre-existing trends. Setting Automated healthcare claims data (2000-10) derived from the virtual data warehouse of 11 health plans in the US Mental Health Research Network. Participants Study cohorts included adolescents (around 1.1 million), young adults (around 1.4 million), and adults (around 5 million). Main outcome measures Rates of antidepressant dispensings, psychotropic drug poisonings (a validated proxy for suicide attempts), and completed suicides. Results Trends in antidepressant use and poisonings changed abruptly after the warnings. In the second year after the warnings, relative changes in antidepressant use were −31.0% (95% confidence interval −33.0% to −29.0%) among adolescents, −24.3% (−25.4% to −23.2%) among young adults, and −14.5% (−16.0% to −12.9%) among adults. These reflected absolute reductions of 696, 1216, and 1621 dispensings per 100 000 people among adolescents, young adults, and adults, respectively. Simultaneously, there were significant, relative increases in psychotropic drug poisonings in adolescents (21.7%, 95% confidence interval 4.9% to 38.5%) and young adults (33.7%, 26.9% to 40.4%) but not among adults (5.2%, −6.5% to 16.9%). These reflected absolute increases of 2 and 4 poisonings per 100 000 people among adolescents and young adults, respectively (approximately 77 additional poisonings in our cohort of 2.5 million young people). Completed suicides did not change for any age group. Conclusions Safety warnings about antidepressants and widespread media coverage decreased antidepressant use, and there were

  9. Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: population based case-control study

    PubMed Central

    Lee, Brian K; Dalman, Christina; Golding, Jean; Lewis, Glyn; Magnusson, Cecilia

    2013-01-01

    Objective To study the association between parental depression and maternal antidepressant use during pregnancy with autism spectrum disorders in offspring. Design Population based nested case-control study. Setting Stockholm County, Sweden, 2001-07. Participants 4429 cases of autism spectrum disorder (1828 with and 2601 without intellectual disability) and 43 277 age and sex matched controls in the full sample (1679 cases of autism spectrum disorder and 16 845 controls with data on maternal antidepressant use nested within a cohort (n=589 114) of young people aged 0-17 years. Main outcome measure A diagnosis of autism spectrum disorder, with or without intellectual disability. Exposures Parental depression and other characteristics prospectively recorded in administrative registers before the birth of the child. Maternal antidepressant use, recorded at the first antenatal interview, was available for children born from 1995 onwards. Results A history of maternal (adjusted odds ratio 1.49, 95% confidence interval 1.08 to 2.08) but not paternal depression was associated with an increased risk of autism spectrum disorders in offspring. In the subsample with available data on drugs, this association was confined to women reporting antidepressant use during pregnancy (3.34, 1.50 to 7.47, P=0.003), irrespective of whether selective serotonin reuptake inhibitors (SSRIs) or non-selective monoamine reuptake inhibitors were reported. All associations were higher in cases of autism without intellectual disability, there being no evidence of an increased risk of autism with intellectual disability. Assuming an unconfounded, causal association, antidepressant use during pregnancy explained 0.6% of the cases of autism spectrum disorder. Conclusions In utero exposure to both SSRIs and non-selective monoamine reuptake inhibitors (tricyclic antidepressants) was associated with an increased risk of autism spectrum disorders, particularly without intellectual disability

  10. Antidepressant use and risk of cardiovascular outcomes in people aged 20 to 64: cohort study using primary care database

    PubMed Central

    Hill, Trevor; Morriss, Richard; Moore, Michael; Arthur, Antony; Hippisley-Cox, Julia

    2016-01-01

    Objective To assess associations between different antidepressant treatments and rates of three cardiovascular outcomes (myocardial infarction, stroke or transient ischaemic attack, and arrhythmia) in people with depression. Design Cohort study. Setting UK general practices contributing to the QResearch primary care database. Participants 238 963 patients aged 20 to 64 years with a first diagnosis of depression between 1 January 2000 and 31 July 2011. Exposures Antidepressant class (tricyclic and related antidepressants, selective serotonin reuptake inhibitors, other antidepressants), dose, duration of use, and commonly prescribed individual antidepressant drugs. Main outcome measures First diagnoses of myocardial infarction, stroke or transient ischaemic attack, and arrhythmia during five years’ follow-up. Cox proportional hazards models were used to estimate hazard ratios, adjusting for potential confounding variables. Results During five years of follow-up, 772 patients had a myocardial infarction, 1106 had a stroke or transient ischaemic attack, and 1452 were diagnosed as having arrhythmia. No significant associations were found between antidepressant class and myocardial infarction over five years’ follow-up. In the first year of follow-up, patients treated with selective serotonin reuptake inhibitors had a significantly reduced risk of myocardial infarction (adjusted hazard ratio 0.58, 95% confidence interval 0.42 to 0.79) compared with no use of antidepressants; among individual drugs, fluoxetine was associated with a significantly reduced risk (0.44, 0.27 to 0.72) and lofepramine with a significantly increased risk (3.07, 1.50 to 6.26). No significant associations were found between antidepressant class or individual drugs and risk of stroke or transient ischaemic attack. Antidepressant class was not significantly associated with arrhythmia over five years’ follow-up, although the risk was significantly increased during the first 28 days of

  11. Emergent Anxiety after Antidepressant Initiation: a Retrospective Cohort Study of Depressed VA Health System Patients

    PubMed Central

    Li, Zhiguo; Pfeiffer, Paul N.; Hoggatt, Katherine J.; Zivin, Kara; Downing, Karen; Ganoczy, Dara; Valenstein, Marcia

    2011-01-01

    Background Initiation of antidepressant treatment for depression may be associated with new onset (emergent) anxiety. Objective We assessed patient demographic and clinical factors associated with emergent anxiety following a new antidepressant start among depressed VA health system patients. Methods Using a retrospective cohort design, we obtained data from 328,888 depressed VA patients newly prescribed one of the seven most commonly used antidepressants between April 1999 and September 2004 from the VA National Depression Registry. We examined the prevalence of emergent anxiety, defined as either a new anxiety diagnoses or by new antianxiety medication starts, in the 12 weeks following new antidepressant start. In multivariate analyses, we assessed the hazard ratios for emerging anxiety associated with patient characteristics and specific antidepressant agents. Results Approximately 3% patients developed clinically significant anxiety within 12 weeks of starting an antidepressant. Younger age (age <45 years and 45–64 years) was associated with higher risks for emergent anxiety than older age (≥65 years) (HR: 1.72 and 1.55, 95% CI: 1.59–1.85, and 1.38–1.72, respectively). Female gender was associated with higher risks than male gender (HR: 1.17, 95% CI: 1.10–1.26), and white and other races compared with black race were associated with higher risks of emergent anxiety (HR: 1.49 and 1.13, 95% CIs: 1.30–1.59 and 1.04–1.23, respectively). Finally, antidepressant fills occurring in years subsequent to 1999 were associated with lower risks of emergent anxiety. Conclusions Only a small proportion of patients developed emergent anxiety following a new antidepressant start, resulting in a new diagnosis or antianxiety medication use. Anxiety occurred more often in young adults, whites, and women. PMID:22177372

  12. What factors influence long-term antidepressant use in primary care? Findings from the Australian diamond cohort study.

    PubMed

    Ambresin, Gilles; Palmer, Victoria; Densley, Konstancja; Dowrick, Christopher; Gilchrist, Gail; Gunn, Jane M

    2015-05-01

    Antidepressants are one of the most commonly prescribed drugs in primary care. The rise in use is mostly due to an increasing number of long-term users of antidepressants (LTU AD). Little is known about the factors driving increased long-term use. We examined the socio-demographic, clinical factors and health service use characteristics associated with LTU AD to extend our understanding of the factors that may be driving the increase in antidepressant use. Cross-sectional analysis of 789 participants with probable depression (CES-D≥16) recruited from 30 randomly selected Australian general practices to take part in a ten-year cohort study about depression were surveyed about their antidepressant use. 165 (21.0%) participants reported <2 years of antidepressant use and 145 (18.4%) reported ≥2 years of antidepressant use. After adjusting for depression severity, LTU AD was associated with: single (OR 1.56, 95%CI 1.05-2.32) or recurrent episode of depression (3.44, 2.06-5.74); using SSRIs (3.85, 2.03-7.33), sedatives (2.04, 1.29-3.22), or antipsychotics (4.51, 1.67-12.17); functional limitations due to long-term illness (2.81, 1.55-5.08), poor/fair self-rated health (1.57, 1.14-2.15), inability to work (2.49, 1.37-4.53), benefits as main source of income (2.15, 1.33-3.49), GP visits longer than 20min (1.79, 1.17-2.73); rating GP visits as moderately to extremely helpful (2.71, 1.79-4.11), and more self-help practices (1.16, 1.09-1.23). All measures were self-report. Sample may not be representative of culturally different or adolescent populations. Cross-sectional design raises possibility of "confounding by indication". Long-term antidepressant use is relatively common in primary care. It occurs within the context of complex mental, physical and social morbidities. Whilst most long-term use is associated with a history of recurrent depression there remains a significant opportunity for treatment re-evaluation and timely discontinuation. Copyright © 2015 Elsevier

  13. Understanding the prescription of antidepressants: a Qualitative study among French GPs

    PubMed Central

    2011-01-01

    Background One-tenth of France's population is prescribed at least one antidepressant, primarily by General Practitioners. The reasons for this high prescription rate remain unclear. One-third of these prescriptions may not comply with clinical practice guidelines, and 20% are potentially unrelated to any psychiatric condition. Our aim was to explore how GPs declare they use antidepressants in daily practice and understand their reasons for prescribing them. Method Six focus groups including a total of 56 rural and urban GPs, with four interviews were performed. The topic guide focused on reasons for prescribing antidepressants in various primary care situations. Phenomenological analysis was performed by four researchers. Results Antidepressants were seen as useful and not harmful. Personal assessment based on experience and feeling determined the GPs' decisions rather than the use of scales. Twenty-four "non-psychiatric" conditions possibly leading to prescription of antidepressants in primary care were found. Conclusions The GPs reported prescribing antidepressants for a wide range of conditions other than depression. The GPs' decision making process is difficult and complex. They seemed to prefer to focus on their difficulties in diagnosing depression rather than on useless overtreatment. Instead of using the guidelines criteria to detect potential cases of useful prescription, physicians tend to use their own tools based on gut feelings, knowledge of the patient and contextual issues. PMID:21943348

  14. The tail suspension test as a model for assessing antidepressant activity: review of pharmacological and genetic studies in mice.

    PubMed

    Cryan, John F; Mombereau, Cedric; Vassout, Annick

    2005-01-01

    Since its introduction almost 20 years ago, the tail suspension test has become one of the most widely used models for assessing antidepressant-like activity in mice. The test is based on the fact that animals subjected to the short-term, inescapable stress of being suspended by their tail, will develop an immobile posture. Various antidepressant medications reverse the immobility and promote the occurrence of escape-related behaviour. This review focuses on the utility this test as part of a research program aimed at understanding the mechanism of action of antidepressants. We discuss the inherent difficulties in modeling depression in rodents. We describe how the tail suspension differs from the closely related forced swim test. Further, we address some key issues associated with using the TST as a model of antidepressant action. We discuss issues regarding whether it satisfies criteria to be a valid model for assessing depression-related behavioural traits. We elaborate on the tests' ease of use, strain differences observed in the test and gender effects in the test. We focus on the utility of the test for genetic analysis. Furthermore, we discuss the concept of whether immobility maybe a behavioural trait relevant to depression. All of the available pharmacological data using the test in genetically modified mice is collated. Special attention is given to selective breeding programs such as the Rouen 'depressed' mice which have been bred for high and low immobility in the tail suspension test. We provide an extensive pooling of the pharmacological studies published to date using the test. Finally, we provide novel pharmacological validation of an automated system (Bioseb) for assessing immobility. Taken together, we conclude that the tail suspension test is a useful test for assessing the behavioural effects of antidepressant compounds and other pharmacological and genetic manipulations relevant to depression.

  15. Stress resilience in adolescence and subsequent antidepressant and anxiolytic medication in middle aged men: Swedish cohort study.

    PubMed

    Hiyoshi, Ayako; Udumyan, Ruzan; Osika, Walter; Bihagen, Erik; Fall, Katja; Montgomery, Scott

    2015-06-01

    It is unclear whether psychological resilience to stress in adolescence represents a persistent characteristic relevant to the subsequent risk for depression and anxiety in later adulthood. We aimed to test whether low psychological stress resilience assessed in adolescence is associated with an increased risk of receiving medication for depression and anxiety in middle age. We utilized Swedish register-based cohort study. Men born between 1952 and 1956 (n = 175,699), who underwent compulsory assessment for military conscription in late adolescence were followed to examine subsequent risk of pharmaceutically-treated depression and anxiety in middle age, from 2006 to 2009 corresponding to ages between 50 and 58 years, using Cox regression. The associations of stress resilience with prescription of antidepressant and anxiolytics medication through potential mediating factors cognitive and physical function and adult socioeconomic factors were calculated. Low stress resilience was associated with elevated risks for antidepressant (hazard ratio (HR):1.5 (95% CI 1.4 1.6)) and anxiolytics (HR:2.4 (CI 2.0 2.7)) medication. Adjustment for measures of childhood living circumstances attenuated the associations somewhat. Around a third of association with low stress resilience, and a half of that with moderate resilience, was mediated through cognitive and physical function in adolescence and adult socioeconomic factors. The magnitude of the inverse association of higher cognitive function with antidepressant medication was eliminated among those with low stress resilience. These results indicate that low stress resilience in adolescence is associated with an increased risk for antidepressant and anxiolytics medication over 30 years later, in part mediated through developmental factors in adolescence and socioeconomic circumstances in adulthood, and low stress resilience can diminish or eliminate the inverse association of higher cognitive function with antidepressant

  16. [Do depressed patients comply with treatments prescribed?: a cross-sectional study of adherence to the antidepressant treatment].

    PubMed

    Oller-Canet, Silvia; Fernández-San Martín, Maria I; García-Lecina, Raquel; Castro Rodríguez, Jose I; Font-Canal, Teresa; Lacasta-Tintorer, David; Martín-López, Luis M; Flamarich-Zampalo, David

    2011-01-01

    INTRODUCTION. Compliance with antidepressant treatment is a very relevant factor in the outcome of depressive disorders. Poor compliance has been associated with worse outcome, increased rate of relapses and greater cost. This study has aimed to describe adherence to antidepressant treatment in a sample of primary care patients with a diagnosis of depression in 2007. METHODS. Randomized sampling was made of patients with depression and antidepressant treatment attended in two primary care teams. Their medical records were reviewed to obtain the total number of prescriptions given to patients and the total number of prescriptions dispensed in the pharmacies. The difference between prescriptions written and collected was calculated. A difference of ± 2 was considered as good compliance. Results are shown as percentages. Comparisons were made with the chi-square, Student’s T and ANOVA tests, where appropriate. RESULTS. The simple was made up of 212 patients. Mean age was 63.2 years (SD 15.27). In the sample, 66.5% were treated with only one antidepressant and 24.1% with two. The percentage of non-compliance was 33.96% (95% CI: 25.35–40.57). Treatment-adherent patients have a lower percentage of long-term treatment with other drugs. The percentage of treatment-adherent women was higher than non-adherent (p=0.015). No differences were found in compliance among patients treated in the mental health center. CONCLUSIONS. One third of patients on antidepressant drug treatment were non-compliers because the drugs were not picked up properly from the pharmacies. We need to develop strategies to improve the therapeutic adherence of patients.

  17. How Commonly Used Inclusion and Exclusion Criteria in Antidepressant Registration Trials Affect Study Enrollment.

    PubMed

    Preskorn, Sheldon H; Macaluso, Matthew; Trivedi, Madhukar

    2015-07-01

    In clinical trials, each specific inclusion and exclusion criterion eliminates a percentage of the potentially eligible population from trial participation and thus increases the time and effort needed for enrollment in a study. Drug developers often do not have data on how these criteria affect the pool of potentially eligible subjects for their trials and, hence, they cannot factor in the impact of these criteria when designing a study and planning the time needed to complete it. Consequently, drug developers often have ambitious timelines that are unrealistic and can lead to actions that may interfere with the ability to separate the efficacy of drug versus placebo. To investigate the effects of inclusion and exclusion criteria on study enrollment, the authors quantified the effects of the inclusion and exclusion criteria commonly used in antidepressant registration trials (ARTs) by applying these criteria to the population treated in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. In essence, the STAR*D study population was used as a surrogate for the general population of individuals with major depressive disorder. The effect of each criterion commonly used in ARTs was assessed in terms of the percentage of the STAR*D population that would have been excluded individually and collectively (i.e., when all criteria were applied at once). For continuous criteria such as age and severity of depression, the resulting effects have been presented graphically. Collectively, the typical inclusion and exclusion criteria used in ARTs would have eliminated at least 82% of the STAR*D population. This result means that more than 5 times the number of subjects would have to be screened to find a population that would meet the typical inclusion and exclusion criteria for an ART, directly determining the screening effort required in terms of both resources and time. Thus, developers of antidepressant drugs can use the data from this study to plan the

  18. Delineation of molecular pathway activities of the chronic antidepressant treatment response suggests important roles for glutamatergic and ubiquitin–proteasome systems

    PubMed Central

    Park, D I; Dournes, C; Sillaber, I; Ising, M; Asara, J M; Webhofer, C; Filiou, M D; Müller, M B; Turck, C W

    2017-01-01

    The aim of this study was to identify molecular pathways related to antidepressant response. We administered paroxetine to the DBA/2J mice for 28 days. Following the treatment, the mice were grouped into responders or non-responders depending on the time they spent immobile in the forced swim test. Hippocampal metabolomics and proteomics analyses revealed that chronic paroxetine treatment affects glutamate-related metabolite and protein levels differentially in the two groups. We found significant differences in the expression of N-methyl-d-aspartate receptor and neuronal nitric oxide synthase proteins between the two groups, without any significant alterations in the respective transcript levels. In addition, we found that chronic paroxetine treatment altered the levels of proteins associated with the ubiquitin–proteasome system (UPS). The soluble guanylate cyclase-β1, proteasome subunit α type-2 and ubiquitination levels were also affected in peripheral blood mononuclear cells from antidepressant responder and non-responder patients suffering from major depressive disorder. We submit that the glutamatergic system and UPS have a crucial role in the antidepressant treatment response in both mice and humans. PMID:28375208

  19. Combined rasagiline and antidepressant use in Parkinson disease in the ADAGIO study: effects on nonmotor symptoms and tolerability.

    PubMed

    Smith, Kara M; Eyal, Eli; Weintraub, Daniel

    2015-01-01

    Depression, cognitive impairment, and other nonmotor symptoms (NMSs) are common early in Parkinson disease (PD) and may be in part due to disease-related dopamine deficiency. Many patients with PD are treated with antidepressants for NMSs, and the effect of the combination of PD medications that enhance dopamine neurotransmission and antidepressants on NMSs has not been studied. We report the effects of the addition of a monoamine oxidase B inhibitor, rasagiline, to antidepressant treatment in PD. To evaluate the effect of rasagiline on depression, cognition, and other PD NMSs in patients taking an antidepressant in the Attenuation of Disease Progression With Azilect Given Once Daily (ADAGIO) study. The ADAGIO study was a double-blind, placebo-controlled, delayed-start trial of rasagiline in de novo PD. In this exploratory post hoc analysis, we analyzed patients taking an antidepressant during the 36-week phase 1 period, in which patients were randomized to rasagiline (1 or 2 mg/d) or placebo. We evaluated the change in NMSs in patients taking an antidepressant and rasagiline compared with those taking placebo. The NMSs were assessed by Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale Nonmotor Experiences of Daily Living, the original Unified Parkinson's Disease Rating Scale, and the Parkinson Fatigue Scale. A total of 191 of the 1174 patients (16.3%) were treated with antidepressants during phase 1 and provided efficacy data. Depression and cognition scores revealed significantly less worsening in the rasagiline group compared with the placebo group (differences in Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale item-adjusted means [SEs], -0.19 [0.10], P = .048, and -0.20 [0.05], P < .001, respectively). Parkinson Fatigue Scale (mean [SE] difference, -0.42 [0.09], P < .001) and daytime sleepiness (mean [SE] difference, -0.24 [0.09], P = .006) scores also revealed

  20. Use of antidepressants and the risk of myocardial infarction in middle-aged and older adults: a matched case-control study.

    PubMed

    Noordam, Raymond; Aarts, Nikkie; Leening, Maarten J G; Tiemeier, Henning; Franco, Oscar H; Hofman, Albert; Stricker, Bruno H; Visser, Loes E

    2016-02-01

    Antidepressants, specifically selective serotonin reuptake-inhibiting antidepressants (SSRIs), decrease platelet activation and aggregation in in vitro experiments and could therefore decrease the risk of myocardial infarction (MI). However, prior studies addressing this hypothesis showed contradictory results. Our purpose was to investigate the association between the use of any antidepressant drug and incident MI among middle-aged and older adults. We embedded a case-control study in the prospective Rotterdam Study (1991-2011). Controls were matched to MI cases based on sex and age at the same calendar date, and confounding factors were taken into account as time-varying covariates. The relative risk of MI during current and past use of an antidepressant was analyzed with conditional logistic regression with never use of antidepressant drugs as the reference category. A total of 744 out of a cohort of 9499 study participants developed MI during follow-up. After statistical adjustment for traditional cardiovascular risk factors and depression, current use of any antidepressant was associated with a lower risk of MI (odds ratio (OR), 0.71; 95 % confidence interval (CI), 0.51-0.98) compared with never use of any antidepressant. SSRI use showed the lowest relative risk (OR, 0.65; 95 % CI, 0.41-1.02), albeit marginally not statistically significant. Past use of any of the antidepressant classes was not associated with a lower risk of MI. Current use of antidepressants was associated with a lower risk of MI. Of the different classes, the use of SSRIs showed the lowest risk of MI, and therefore confirming the research hypothesis.

  1. Antidepressants and Weight Gain

    MedlinePlus

    Diseases and Conditions Depression (major depressive disorder) Can antidepressants cause weight gain? Answers from Daniel K. Hall- ... is a possible side effect of nearly all antidepressants. However, each person responds to antidepressants differently. Some ...

  2. Inclusion/exclusion criteria in placebo-controlled studies of vortioxetine: Comparison to other antidepressants and implications for product labeling.

    PubMed

    Zimmerman, Mark; Clark, Heather L; Multach, Matthew D; Walsh, Emily; Rosenstein, Lia K; Gazarian, Douglas

    2016-01-15

    We recently conducted a comprehensive review of the psychiatric inclusion/exclusion criteria used in 170 placebo-controlled antidepressant efficacy trials (AETs) published during the past 20 years and found that the criteria of more recent studies were significantly more restrictive than prior studies. Vortioxetine is the most recently approved medication for the treatment of major depressive disorder (MDD). We compared the inclusion/exclusion criteria of the vortioxetine studies to the criteria used in other AETs, and discuss the broader issue of the generalizability of AETs and the implications this might have for the labeling of antidepressants receiving FDA approval. We conducted a comprehensive literature review of placebo-controlled AETs published from January, 1995 through December, 2014. We identified 170 AETs published during this 20 year period and compared the inclusion/exclusion criteria used in the 12 studies of vortioxetine to those used in the nonvortioxetine studies. A second analysis compared vortioxetine to the 3 antidepressants most recently approved prior to vortioxetine (desvenlafaxine, levomilnacipran extended release, vilazodone). Compared to the nonvortioxetine AETs, the vortioxetine studies significantly more often excluded patients with any comorbid Axis I disorder (p<.001) and more often required the current depressive episode to be longer than the DSM minimum symptom duration requirement of 2 weeks (p<.01). The cutoff on the Montgomery Asberg Depression Rating Scale required for inclusion in the vortioxetine studies was higher than the cutoff used in the other AETs (p<.01). A limitation of the present analysis is that it was based on published placebo-controlled studies of antidepressants. The inclusion/exclusion criteria in the studies of vortioxetine were more restrictive than the criteria used in other AETs. Inconsistent with FDA guidelines on the labeling of medications, the label of vortioxetine does not include a description of the

  3. Stressful life events and social health factors in women using anxiolytics and antidepressants: an Italian observational study in community pharmacies.

    PubMed

    D'Incau, Paola; Barbui, Corrado; Tubini, Jacopo; Conforti, Anita

    2011-04-01

    In Italy, as in all of Europe, women differ from men in that they are somewhat more sensitive to the depressogenic effects of stressful life events related to their social networks and emotional sphere. Women are more likely than men to have experienced poverty, gender discrimination, and physical and sexual abuse. The purpose of this study was to expand the knowledge about the occurrence of stressful life events in women exposed and not exposed to anxiolytics and antidepressants in a community pharmacy setting. Women attending 100 community pharmacies in the Italian Veneto region were surveyed by pharmacists with regard to a number of general features of their current pharmacologic treatment. Women independently completed a written self-assessment questionnaire that focused on stressful life events. Unconditional logistic regression analysis was performed to investigate the association between anxiolytics and antidepressants use and potential factors, including stressful life events. The study population comprised 11,357 women. One or more stressful life events occurred in 90% of the women treated with anxiolytics and/or antidepressants (users [n = 3848]) and in 74% of the women not treated with these drugs (nonusers [n = 7509]) (odds ratio = 3.19; 95% CI, 2.83-3.60). On average, the life events occurred during the previous 6 months and the women considered the influence of these events on their well-being to be severe. After the unconditional logistic regression analysis, the association between anxiolytics and/or antidepressants use remained positive for most of the stressful life events studied as well as for other factors: separation/divorce, living alone or with others (family or friends), unemployment, whether currently being seen by a psychologist/psychiatrist, and treatment with drugs for the alimentary tract and metabolism, cardiovascular system, or nervous system. A significant association between stressful life events and anxiolytics and

  4. Segregating the cerebral mechanisms of antidepressants and placebo in fibromyalgia.

    PubMed

    Jensen, Karin B; Petzke, Frank; Carville, Serena; Choy, Ernest; Fransson, Peter; Gracely, Richard H; Vitton, Olivier; Marcus, Hanke; Williams, Steven C R; Ingvar, Martin; Kosek, Eva

    2014-12-01

    Antidepressant drugs are commonly used to treat fibromyalgia, but there is little knowledge about their mechanisms of action. The aim of this study was to compare the cerebral and behavioral response to positive treatment effects of antidepressants or placebo. Ninety-two fibromyalgia patients participated in a 12-week, double-blind, placebo-controlled clinical trial with milnacipran, a serotonin-norepinephrine reuptake inhibitor. Before and after treatment, measures of cerebral pain processing were obtained using functional magnetic resonance imaging. Also, there were stimulus response assessments of pressure pain, measures of weekly pain, and fibromyalgia impact. Following treatment, milnacipran responders exhibited significantly higher activity in the posterior cingulum compared with placebo responders. The mere exposure to milnacipran did not explain our findings because milnacipran responders exhibited increased activity also in comparison to milnacipran nonresponders. Stimulus response assessments revealed specific antihyperalgesic effects in milnacipran responders, which was also correlated with reduced clinical pain and with increased activation of the posterior cingulum. A short history of pain predicted positive treatment response to milnacipran. We report segregated neural mechanisms for positive responses to treatment with milnacipran and placebo, reflected in the posterior cingulum. The increase of pain-evoked activation in the posterior cingulum may reflect a normalization of altered default mode network processing, an alteration implicated in fibromyalgia pathophysiology. This study presents neural and psychophysical correlates to positive treatment responses in patients with fibromyalgia, treated with either milnacipran or placebo. The comparison between placebo responders and milnacipran responders may shed light on the specific mechanisms involved in antidepressant treatment of chronic pain. Copyright © 2014 American Pain Society. Published by

  5. Exclusion criteria used in antidepressant efficacy trials: consistency across studies and representativeness of samples included.

    PubMed

    Zimmerman, Mark; Chelminski, Iwona; Posternak, Michael A

    2004-02-01

    The inclusion and exclusion criteria used to select subjects for participation in antidepressant efficacy trials (AETs) vary from study to study. It is unknown how much impact different sets of exclusion criteria have on the representativeness of subjects treated in AETs. In the present study, we applied the inclusion and exclusion criteria used in 39 recently published AETs to patients evaluated in routine clinical practice to evaluate the range and extent of the representativeness of samples treated in AETs. Nearly 600 patients with DSM-IV major depressive disorder (MDD) or bipolar depression underwent a thorough diagnostic evaluation. Inclusion and exclusion criteria used in AETs were applied to determine how many patients from our sample would have qualified for each AET had they applied. Approximately one sixth of the 596 depressed patients would have been excluded from an efficacy trial because they had a bipolar or psychotic subtype of depression. In the remaining 503 outpatients with nonpsychotic, unipolar MDD, the rates of exclusion ranged from 0% to 95.0% (mean=65.8%). Thus, the findings suggest that there is much variability in the generalizability of AETs, although, in general, subjects treated in AETs represent only a minority of patients treated for MDD in a community-based psychiatry outpatient practice.

  6. Nonresponders to pharyngeal surgery for obstructive sleep apnea: insights from drug-induced sleep endoscopy

    PubMed Central

    Kezirian, Eric J.

    2011-01-01

    Objectives/Hypothesis To examine DISE findings in nonresponders to previous pharyngeal OSA surgery Study Design cross-sectional Methods Drug-induced sleep endoscopy (DISE) using propofol for unconscious sedation was performed in nonresponders to previous OSA surgery (including palate surgery with or without tonsillectomy and possible other procedures), defined by an apnea-hypopnea index >10 events/hour. Recorded findings included the presence and degree of obstruction in the palatal and hypopharyngeal regions, the contributions of specific structures (velum, oropharyngeal lateral walls, tongue, and/or epiglottis) to upper airway obstruction, and the degree of mouth opening. Results Thirty-three nonresponders underwent DISE examinations. Age was 46.2±11.8 years, and 9% (3/33) were female. On diagnostic sleep studies prior to DISE, the apnea-hypopnea index was 43.4±26.6 events/hour. During DISE, a majority of subjects demonstrated residual palatal obstruction, and almost all demonstrated hypopharyngeal obstruction. A diversity of individual structures contributed to upper airway obstruction, often in combination. Moderate to severe mouth opening occurred in one-third of subjects and was associated with narrowing of upper airway dimensions. Conclusions Residual upper airway obstruction in surgery nonresponders likely occurs due to multiple mechanisms, and DISE may enhance the understanding of them. PMID:21557231

  7. Pharmacoinformatic and molecular docking studies reveal potential novel antidepressants against neurodegenerative disorders by targeting HSPB8.

    PubMed

    Sehgal, Sheikh Arslan; Mannan, Shazia; Ali, Sannia

    2016-01-01

    Charcot-Marie-Tooth (CMT) disease is an inherited peripheral neuromuscular disorder characterized by length-dependent and progressive degeneration of peripheral nerves, leading to muscular weakness. Research has shown that mutated HSPB8 may be responsible for depression, neurodegenerative disorders, and improper functioning of peripheral nerves, resulting in neuromuscular disorders like CMT. In the current work, a hybrid approach of virtual screening and molecular docking studies was followed by homology modeling and pharmacophore identification. Detailed screening analyses were carried out by 2-D similarity search against prescribed antidepressant drugs with physicochemical properties. LigandScout was employed to ascertain novel molecules and pharmacophore properties. In this study, we report three novel compounds that showed maximum binding affinity with HSPB8. Docking analysis elucidated that Met37, Ser57, Ser58, Trp60, Thr63, Thr114, Lys115, Asp116, Gly117, Val152, Val154, Leu186, Asp189, Ser190, Gln191, and Glu192 are critical residues for ligand-receptor interactions. Our analyses suggested paroxetine as a potent compound for targeting HSPB8. Selected compounds have more effective energy scores than the selected drug analogs. Additionally, site-directed mutagenesis could be significant for further analysis of the binding pocket. The novel findings based on an in silico approach may be momentous for potent drug design against depression and CMT.

  8. Pharmacoinformatic and molecular docking studies reveal potential novel antidepressants against neurodegenerative disorders by targeting HSPB8

    PubMed Central

    Sehgal, Sheikh Arslan; Mannan, Shazia; Ali, Sannia

    2016-01-01

    Charcot–Marie–Tooth (CMT) disease is an inherited peripheral neuromuscular disorder characterized by length-dependent and progressive degeneration of peripheral nerves, leading to muscular weakness. Research has shown that mutated HSPB8 may be responsible for depression, neurodegenerative disorders, and improper functioning of peripheral nerves, resulting in neuromuscular disorders like CMT. In the current work, a hybrid approach of virtual screening and molecular docking studies was followed by homology modeling and pharmacophore identification. Detailed screening analyses were carried out by 2-D similarity search against prescribed antidepressant drugs with physicochemical properties. LigandScout was employed to ascertain novel molecules and pharmacophore properties. In this study, we report three novel compounds that showed maximum binding affinity with HSPB8. Docking analysis elucidated that Met37, Ser57, Ser58, Trp60, Thr63, Thr114, Lys115, Asp116, Gly117, Val152, Val154, Leu186, Asp189, Ser190, Gln191, and Glu192 are critical residues for ligand–receptor interactions. Our analyses suggested paroxetine as a potent compound for targeting HSPB8. Selected compounds have more effective energy scores than the selected drug analogs. Additionally, site-directed mutagenesis could be significant for further analysis of the binding pocket. The novel findings based on an in silico approach may be momentous for potent drug design against depression and CMT. PMID:27226709

  9. [Mirtazapine versus other antidepressive agents for depression].

    PubMed

    Knud Larsen, Jens

    2012-11-12

    A Cochrane analysis compared efficacy and side effects of mirtazapine with other antidepressants. After six weeks of treatment no reliable difference of efficacy between mirtazapine, selective serotonin reuptake inhibitors (SSRI), noradrenaline reuptake inhibitors or tricyclic antidepressants was found. The side effects like increased sleep and weight gain were compared by treatment with mirtazapine and treatment with SSRI antidepressants. The very fact of the sleep effect and the fast onset of action have probably increased the effect size compared with SSRI antidepressants. The results of the Cochrane analysis cannot for certain be generalized to inpatients, as other studies have found tricyclic antidepressants to be especially effective.

  10. Longitudinal association of antidepressant medication use with metabolic syndrome: Results of a 9-year follow-up of the D.E.S.I.R. cohort study.

    PubMed

    Azevedo Da Silva, Marine; Balkau, Beverley; Roussel, Ronan; Tichet, Jean; Fumeron, Frédéric; Fagherazzi, Guy; Nabi, Hermann

    2016-12-01

    To examine longitudinal associations between antidepressant medication use and the metabolic syndrome (MetS). 5014 participants (49.8% were men) from the D.E.S.I.R. cohort study, aged 30-65 years at baseline in 1994-1996, were followed over 9 years at 3-yearly intervals (1997-1999, 2000-2002, and 2003-2005). Antidepressant use and MetS, defined by the National Cholesterol Education Program Adult Treatment Panel III criteria (NCEP-ATP III) and the American Heart Association and the National Heart, Lung and Blood Institute (AHA/NHLBI) criteria, were assessed concurrently at four medical examinations. In fully-adjusted longitudinal logistic regression analyses based on generalized estimating equations, antidepressant users had a 9% (p=0.011) and a 6% (p=0.036) greater annual increase in the odds of having the MetS defined by NCEP-ATP III and AHA/NHLBI criteria respectively. Sex-specific analyses showed that this association was confined to men only. When the different types of antidepressant were considered, men who used selective serotonin reuptake inhibitors (SSRIs), imipramine type antidepressants or "other" antidepressants had a 52% (p=0.028), 31% (p=0.011), and 16% (p=0.016) greater annual increase in the odds of having the MetS over time compared to non-users, respectively. These associations depended on the definition of the MetS. Our longitudinal data showed that antidepressant use was associated with an increased odds of having the MetS in men but not in women and this was mainly for SSRIs, imipramine type and "other" antidepressants. People on antidepressants may need to be checked regularly for the elements of the metabolic syndrome treatable by change in diet, physical activity and/or by medication therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Tricyclic Antidepressants

    NASA Astrophysics Data System (ADS)

    Schmidt, Gary J.

    The use of tricyclic antidepressant drugs is becoming increasingly prevalent for the treatment of depressed patients. It has been suggested that, analogous to many other drug substances, the tricyclic drugs exhibit clinical effectiveness within a defined therapeutic concentration range (1-10). Very recently, both Dito (11) and Orsulak and Schildkraut (12) have summarized the usefulness of measuring serum concentrations of these drugs. These authors suggest that knowledge of the plasma concentrations of these drugs aid the physician in determining patient compliance and initiating the best possible drug treatment.

  12. The antidepressant effect of musk in an animal model of depression: a histopathological study.

    PubMed

    Ayuob, Nasra Naeim; Ali, Soad Shaker; Suliaman, Mansour; El Wahab, Manal Galal Abd; Ahmed, Samra Mansour

    2016-11-01

    Depression is a significant public health concern all over the world, especially in modern communities. This study aims to assess the efficacy of musk in alleviating the behavioral, biochemical and histopathological changes induced by chronic unpredictable mild stress (CUMS) in an animal model of depression and to explore the underlying mechanism of this effect. Male Swiss albino mice were divided into four groups (n = 10): control, CUMS, CUMS+fluoxetine and CUMS+musk. At the end of the experiment, behavioral tests were administered and serum corticosterone and testosterone levels were assessed. Surface markers, proteins and gene expressions of brain-derived neurotropic factor (BDNF) and glucocorticoid receptors (GRs) in the hippocampus were assessed. The immunoexpression of glial fibrillary acidic protein, Ki67 and caspase-3 was also assessed. Data were analyzed using the Statistical Package for the Social Sciences and a P value of less than 0.05 was considered significant. Musk alleviated the behavioral changes caused by CUMS and reduced elevated corticosterone levels. It reduced CUMS-induced neuronal atrophy in the CA3 and dentate gyrus of the hippocampus and restored astrocytes. Musk reduced the neuro- and glial apoptosis observed in stressed mice in a manner comparable to that of fluoxetine. Musk induced these effects through up-regulating both BDNF and GR gene and protein expressions. Musk has an antidepressant-like effect in an animal model of depression, so it is advisable to assess its efficacy in people continually exposed to stressors.

  13. Retrospective pilot study for analysis of antidepressant serum concentrations of citalopram and venlafaxine during inflammation.

    PubMed

    Hefner, G; Shams, M E E; Unterecker, S; Falter, T; Hiemke, C

    2015-09-01

    Inflammation-mediated changes in drug metabolism may increase drug levels in blood and lead to intoxications. The objective of this study was to find out whether elevated serum levels of C-reactive protein (CRP) are associated with increased serum concentrations of the antidepressants citalopram and venlafaxine. Therapeutic drug monitoring request forms of psychiatric patients were screened retrospectively. The serum concentrations in relation to the daily doses [(C/D) (ng/ml/mg)] and the metabolic ratios (metabolite/drug) were compared intraindividually under normal (<5 mg/l) and pathological (>5 mg/l) condition by the Wilcoxon signed-rank test. Elevated levels of CRP were not associated with a significant (P>0.05) increase in C/D for citalopram (2.4 ng/ml/mg vs. 2.85 ng/ml/mg, N=15) or in C/D for the active moiety of venlafaxine (1.76 ng/ml/mg vs. 1.68 ng/ml/mg, N=39), compared with normal CRP serum levels. No significant difference in the metabolic ratio was observed in both groups. There was no major effect of inflammation on the metabolism of citalopram and venlafaxine. Because of the broad therapeutic indices of these 2 drugs, the drugs seem to be a good choice for the treatment of depression, even if an infection occurs. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Antidepressants and risk of dementia in migraine patients: A population-based case-control study.

    PubMed

    Lee, Cynthia Wei-Sheng; Lin, Cheng-Li; Lin, Pan-Yen; Thielke, Stephen; Su, Kuan-Pin; Kao, Chia-Hung

    2017-04-07

    To ascertain the relationship between receipt of antidepressant agents and the risk of subsequent dementia in migraine patients. A population-based case-control analysis, using the Taiwan National Health Insurance Research Database. We identified 1774 patients with dementia and 1774 matched nondementia controls from migraine patients enrolled in the Taiwan National Health Insurance program between 2005 and 2011. The proportional distributions of exposure to three classes of antidepressant were compared between dementia and nondementia groups. Univariable and multivariable logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of dementia based on antidepressant exposure. The proportions of subjects taking tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and new-generation antidepressants (NGAs) in dementia versus nondementia groups are 52.3 vs 51.2%, 25.5 vs 30.7%, and 18.8 vs 6.26%, respectively. The adjusted ORs of dementia were 1.02 (95% CI=0.89, 1.17; P=0.56) for TCAs, 0.58 (95% CI=0.50, 0.69; P<0.001) for SSRIs, and 4.23 (95% CI=3.34, 5.37; P<0.001) for NGAs. Treatment with SSRIs was associated with a decreased risk of dementia in migraine patients. TCAs showed no association with dementia risk, and NGAs showed increased risk. Given the possibility of confounding by indication, additional prospective trials and basic research are needed before drawing conclusions about the population-level risks for dementia onset conferred by antidepressant medications.

  15. Divergent topological architecture of the default mode network as a pretreatment predictor of early antidepressant response in major depressive disorder

    PubMed Central

    Hou, Zhenghua; Wang, Zan; Jiang, Wenhao; Yin, Yingying; Yue, Yingying; Zhang, Yuqun; Song, Xiaopeng; Yuan, Yonggui

    2016-01-01

    Identifying a robust pretreatment neuroimaging marker would be helpful for the selection of an optimal therapy for major depressive disorder (MDD). We recruited 82 MDD patients [n = 42 treatment-responsive depression (RD) and n = 40 non-responding depression (NRD)] and 50 healthy controls (HC) for this study. Based on the thresholded partial correlation matrices of 58 specific brain regions, a graph theory approach was applied to analyse the topological properties. When compared to HC, both RD and NRD patients exhibited a lower nodal degree (Dnodal) in the left anterior cingulate gyrus; as for RD, the Dnodal of the left superior medial orbitofrontal gyrus was significantly reduced, but the right inferior orbitofrontal gyrus was increased (all P < 0.017, FDR corrected). Moreover, the nodal degree in the right dorsolateral superior frontal cortex (SFGdor) was significantly lower in RD than in NRD. Receiver operating characteristic curve analysis demonstrated that the λ and nodal degree in the right SFGdor exhibited a good ability to distinguish nonresponding patients from responsive patients, which could serve as a specific maker to predict an early response to antidepressants. The disrupted topological configurations in the present study extend the understanding of pretreatment neuroimaging predictors for antidepressant medication. PMID:27966645

  16. Major depressive disorder, antidepressant use, and subsequent 2-year weight change patterns in the Netherlands Study of Depression and Anxiety.

    PubMed

    Gibson-Smith, Deborah; Bot, Mariska; Milaneschi, Yuri; Twisk, Jos W; Visser, Marjolein; Brouwer, Ingeborg A; Penninx, Brenda W J H

    2016-02-01

    Although depression and obesity are bidirectionally associated, little is known about weight changes following major depressive disorder (MDD). This study compared 2-year weight changes between patients with current MDD (cMDD), patients with remitted MDD (rMDD), and healthy controls. Additionally, we examined the relationship between antidepressant medication use and 2-year weight change. Data from 2,542 adults aged 18-65 y were sourced from the Netherlands Study of Depression and Anxiety. Data were collected at baseline and after 2, 4, and 6 years (September 2004-April 2013). Depression status (DSM-IV criteria for MDD) was established with the Composite International Diagnostic Interview. Subsequent 2-year weight changes were categorized as weight loss (> 5% loss), weight stable (within 5% weight loss or gain), and weight gain (> 5% gain). The association of depression status with subsequent weight change, with weight stable as reference category, was studied by combining all repeated measurements in a mixed multinomial logistical regression model. cMDD, but not rMDD, was significantly associated with both weight gain and weight loss over a 2-year period after adjustment for covariates (odds ratio [OR] = 1.67; 95% confidence interval [CI], 1.37-2.03; P < .001; and OR = 1.27; 95% CI 1.01-1.61; P = .045, respectively). Antidepressant use was associated with weight gain (SSRIs: OR = 1.26; 95% CI, 1.05-1.52; other antidepressants: OR = 1.36; 95% CI, 1.00-1.84; P < .05 for both), but not after considering depression status. Compared to cMDD patients who lost weight, those who gained weight had lower initial weight, were younger, had more comorbid anxiety disorders, and reported poorer quality of mood and reduced appetite as depressive symptoms. Compared to controls, cMDD participants have greater odds of either gaining or losing weight over a 2-year period, regardless of antidepressant use. © Copyright 2015 Physicians Postgraduate Press, Inc.

  17. The effects of antidepressant treatment on serotonergic and dopaminergic systems in Fawn-Hooded rats: a quantitative autoradiography study.

    PubMed

    Chen, Feng; Lawrence, Andrew J

    2003-06-20

    Fawn-Hooded (FH) rats exhibit a phenotype including depressive behaviour and high alcohol preference, and as such tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) reduce alcohol consumption in this rat strain [Psychiatr. Genet. 12 (2002) 1-16]. However, the neurochemical effects of these antidepressants on monoamine systems in the brain, especially in mesolimbic areas have not been studied in FH rats. Therefore, the present study investigated neurochemical effects of subchronic treatment (10 days) with desipramine (DMI) and sertraline on several neurochemical markers of serotonin and dopamine systems. Binding to these markers including dopamine transporters (DATs), 5-HT transporters (SERTs), 5-HT(1A)- and 5-HT(2A)-receptors in rat brain sections was performed by quantitative autoradiography. The findings from the present study revealed that DMI and sertraline exhibited differential effects on SERTs and DATs in FH rat brain. For example, DMI caused a dramatic up-regulation of DATs whereas sertraline had no effect on DAT binding. In addition, both antidepressants showed some common and some differential effects on the binding to 5-HT(1A)- and 5-HT(2A)-receptors dependent upon region. These data demonstrate that DMI and sertraline differentially effect serotonergic and dopaminergic systems in mesolimbic regions in FH rats, suggesting that there may be different neurochemical mechanisms underlying their efficacy to reduce ethanol consumption in this animal model.

  18. Antidepressant Sales and the Risk for Alcohol-Related and Non-Alcohol-Related Suicide in Finland—An Individual-Level Population Study

    PubMed Central

    Moustgaard, Heta; Joutsenniemi, Kaisla; Myrskylä, Mikko; Martikainen, Pekka

    2014-01-01

    Objectives A marked decline in suicide rates has co-occurred with increased antidepressant sales in several countries but the causal connection between the trends remains debated. Most previous studies have focused on overall suicide rates and neglected differential effects in population subgroups. Our objective was to investigate whether increasing sales of non-tricyclic antidepressants have reduced alcohol- and non-alcohol-related suicide risk in different population subgroups. Methods We followed a nationally representative sample of 950,158 Finnish adults in 1995–2007 for alcohol-related (n = 2,859) and non-alcohol-related (n = 8,632) suicides. We assessed suicide risk by gender and social group according to regional sales of non-tricyclic antidepressants, measured by sold doses per capita, prevalence of antidepressant users, and proportion of antidepressant users with doses reflecting minimally adequate treatment. Fixed-effects Poisson regression models controlled for regional differences and time trends that may influence suicide risk irrespective of antidepressant sales. Results The number of sold antidepressant doses per capita and the prevalence of antidepressant users were unrelated to male suicide risk. However, one percentage point increase in the proportion of antidepressant users receiving minimally adequate treatment reduced non-alcohol-related male suicide risk by one percent (relative risk 0.987, 95% confidence interval 0.976–0.998). This beneficial effect only emerged among men with high education, high income, and employment, among men without a partner, and men not owning their home. Alcohol-related suicides and female suicides were unrelated to all measures of antidepressant sales. Conclusion We found little evidence that increase in overall sales or in the prevalence of non-tricyclic antidepressant users would have caused the fall in suicide rates in Finland in 1995–2007. However, the rise in the proportion of antidepressant

  19. Usefulness of interim analyses in portending study results in antipsychotic and antidepressant trials.

    PubMed

    Rabinowitz, J; Werbeloff, N; Mandel, F; De Ridder, F; Schacht, A; Menard, F; Caears, I; Stauffer, V; Kapur, S

    2015-11-01

    It is unknown whether interim analyses portend final study results. Fatigue, pressure to complete trials and recruitment differences may mitigate against this. We examined the similarity of efficacy results of the first and second half of recruited patients to complete trials and explore possible intervening variables. Using data from the NewMeds repository of patient level data from placebo-controlled randomized trials of antipsychotics (AP) (22 studies, n=7056) and antidepressants (AD) (39 studies, n=12,217) we compared treatment effect size (placebo vs. active treatment) of the first and second half of patients recruited in completed trials. We found that in AP studies median difference in treatment effect between cohorts was -0.03, indicating that overall first and second cohorts yielded similar results. In AD studies, median difference between cohorts was 0.04, indicating that overall the second cohort had slightly larger active-placebo-difference. Overall, on average there were minimal differences in effect size between the first and the second cohorts, and in 30 of 39 trials interim results were a good estimate of the results on the 2nd cohort. In AD trials first and second cohort results were more similar when the proportion of patients per study centre and recruitment time of the two cohorts was similar. Results suggest that interim analyses in AD and AP studies may reliably serve to estimate ultimate effects and, at least in AD trials, are more accurate when the same sites are used to a similar extent and recruitment time of the two consequent cohorts is similar.

  20. Health literacy and antidepressant medication adherence among adults with diabetes: the diabetes study of Northern California (DISTANCE).

    PubMed

    Bauer, Amy M; Schillinger, Dean; Parker, Melissa M; Katon, Wayne; Adler, Nancy; Adams, Alyce S; Moffet, Howard H; Karter, Andrew J

    2013-09-01

    Previous studies have reported that health literacy limitations are associated with poorer disease control for chronic conditions, but have not evaluated potential associations with medication adherence. To determine whether health literacy limitations are associated with poorer antidepressant medication adherence. Observational new prescription cohort follow-up study. Adults with type 2 diabetes who completed a survey in 2006 and received a new antidepressant prescription during 2006-2010 (N = 1,366) at Kaiser Permanente Northern California. Validated three-item self-report scale measured health literacy. Discrete indices of adherence based on pharmacy dispensing data according to validated methods: primary non-adherence (medication never dispensed); early non-persistence (dispensed once, never refilled); non-persistence at 180 and 365 days; and new prescription medication gap (NPMG; proportion of time that the person is without medication during 12 months after the prescription date). Seventy-two percent of patients were classified as having health literacy limitations. After adjusting for sociodemographic and clinical covariates, patients with health literacy limitations had significantly poorer adherence compared to patients with no limitations, whether measured as early non-persistence (46 % versus 38 %, p < 0.05), non-persistence at 180 days (55 % versus 46 %, p < 0.05), or NPMG (41 % versus 36%, p < 0.01). There were no significant associations with primary adherence or non-persistence at 365 days. Poorer antidepressant adherence among adults with diabetes and health literacy limitations may jeopardize the continuation and maintenance phases of depression pharmacotherapy. Findings underscore the importance of national efforts to address health literacy, simplify health communications regarding treatment options, improve public understanding of depression treatment, and monitor antidepressant adherence.

  1. Evaluating patient adherence to antidepressant therapy among uninsured working adults diagnosed with major depression: results of the Texas Demonstration to Maintain Independence and Employment study.

    PubMed

    Nwokeji, Esmond D; Bohman, Thomas M; Wallisch, Lynn; Stoner, Dena; Christensen, Kristin; Spence, Richard R; Reed, Brian C; Ostermeyer, Britta

    2012-09-01

    This study examined antidepressant adherence and persistence among uninsured working adults diagnosed with major depression enrolled in the Texas Demonstration to Maintain Independence and Employment (DMIE) program. Antidepressant adherence was measured between intervention and control cohorts using proportion of days covered (PDC) during a 365-day observation period. Persistence examined duration of time from drug initiation to discontinuation based on a ≥35-day refill supply gap. Older, non-minority patients with higher education were more adherent or persistent to antidepressant therapy. Adjusting for covariates, results showed no significant difference in PDC at the end of 12-months between intervention and control participants (b = .07, P = .054, semi-partial η (2) = .02). Exploratory analysis found subgroup differences in PDC among the study recruitment cohorts. No significant difference between intervention and control groups was found in persistence between the groups. Follow-up investigation is planned to assess the longer term impact of the DMIE program on antidepressant adherence and persistence.

  2. Reciprocal effects of antidepressant treatment on activity and connectivity of the mood regulating circuit: an FMRI study.

    PubMed

    Anand, Amit; Li, Yu; Wang, Yang; Gardner, Kathryn; Lowe, Mark J

    2007-01-01

    It has been hypothesized that one of the effects of antidepressants is to increase functional connectivity between the cortical mood-regulating and the limbic mood-generating regions. One consequence of this antidepressant effect is thought to be decreased limbic activation in response to negative emotional stimuli. Twelve unmedicated unipolar depressed patients and 11 closely matched healthy comparison subjects completed two magnetic resonance imaging (MRI) scanning sessions at baseline and after 6 weeks. Depressed patients received treatment with sertraline between the two sessions. During each MRI session, subjects completed a resting state functional connectivity scan and a conventional block-design negative vs. neutral pictures regional brain activation scan. After 6 weeks of sertraline treatment resting state, functional connectivity between the ACC and limbic regions increased while limbic activation in response to negative versus neutral pictures decreased. The results of this study are consistent with the hypothesis that antidepressant treatment has reciprocal effects on corticolimbic functional connectivity and limbic activation in response to emotional stimuli.

  3. Follow up of patients who start treatment with antidepressants: treatment satisfaction, treatment compliance, efficacy and safety

    PubMed Central

    2013-01-01

    Background Measuring satisfaction with treatment has proved useful to ascertain the treatment features that are most important to the patients, and to explain increased treatment compliance. However, there are few studies that relate satisfaction to other clinical or self-perceived health status indicators. Recent studies have shown the close relationship between satisfaction with treatment, treatment compliance, and effectiveness. This study attempts to design and validate a scale to evaluate satisfaction with antidepressant drug therapy, assess treatment compliance (self-reported, validated questionnaire, drug accountability and electronic monitorization system), assess efficacy in reducing depressive symptoms and safety in patients who initiate antidepressant drug therapy, as well as to establish predictors of satisfaction, compliance and effectiveness with these drugs. Methods/design This is an observational longitudinal study with a cohort of adults initiating treatment with antidepressant drugs. A multi-centre study will be performed in which 20 Primary Care practices from Castilla-La Mancha are expected to participate. An initial interview and follow-up visits at 15 days, 1, 3, 6, 9 and 12 months will be conducted with all study participants. 706 subjects will be studied (95% confidence interval, precision ± 3%, expected rate of non-compliance 50%, expected non-responders and lost to follow up rate 15%). The following measurements will be performed: development and validation of a scale of satisfaction with antidepressant therapy, participant and antidepressant characteristics, treatment compliance evaluation (Haynes-Sackett Test, Morisky-Green Test, drug accountability and Medication Event Monitoring System), depression symptom reduction (Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale), observation of adverse effects, and beliefs about treatment (The Beliefs about Medicines Questionnaire). Discussion Antidepressant drugs are

  4. Strategic use of new generation antidepressants for depression: SUN(^_^)D study protocol

    PubMed Central

    2011-01-01

    Background After more than half a century of modern psychopharmacology, with billions of dollars spent on antidepressants annually world-wide, we lack good evidence to guide our everyday decisions in conducting antidepressant treatment of patients with major depression. First we did not know which antidepressant to use as first line treatment. Second we do not know which dosage we should be aiming at with that antidepressant. Because more than half of the patients with major depression starting treatment do not remit after adequate trial with the first agent, they will need a second line treatment. Dose escalation, augmentation and switching are the three often recommended second line strategies but we do not know which is better than the others. Moreover, we do not know when to start considering this second line treatment. The recently published multiple-treatments meta-analysis of 12 new generation antidepressants has provided some partial answers to the first question. Starting with these findings, this proposed trial aims to establish the optimum 1st line and 2nd line antidepressant treatment strategy among adult patients with a non-psychotic unipolar major depressive episode. Methods SUN(^_^)D, the Strategic Use of New generation antidepressants for Depression, is an assessor-blinded, parallel-group, multi-centre randomised controlled trial. Step I is a cluster-randomised trial comparing titration up to the minimum vs maximum of the recommended dose range among patients starting with sertraline. The primary outcome is the change in the Patient Health Questionnaire (PHQ)-9 scores administered by a blinded rater via telephone at week 1 through 3. Step II is an individually randomised trial comparing staying on sertraline, augmentation of sertraline with mirtazapine, and switching to mirtazapine among patients who have not remitted on the first line treatment by week 3. The primary outcome is the change in the PHQ-9 scores at week 4 through 9. Step III represents

  5. BDNF - a key transducer of antidepressant effects.

    PubMed

    Björkholm, Carl; Monteggia, Lisa M

    2016-03-01

    How do antidepressants elicit an antidepressant response? Here, we review accumulating evidence that the neurotrophin brain-derived neurotrophic factor (BDNF) serves as a transducer, acting as the link between the antidepressant drug and the neuroplastic changes that result in the improvement of the depressive symptoms. Over the last decade several studies have consistently highlighted BDNF as a key player in antidepressant action. An increase in hippocampal and cortical expression of BDNF mRNA parallels the antidepressant-like response of conventional antidepressants such as SSRIs. Subsequent studies showed that a single bilateral infusion of BDNF into the ventricles or directly into the hippocampus is sufficient to induce a relatively rapid and sustained antidepressant-like effect. Importantly, the antidepressant-like response to conventional antidepressants is attenuated in mice where the BDNF signaling has been disrupted by genetic manipulations. Low dose ketamine, which has been found to induce a rapid antidepressant effect in patients with treatment-resistant depression, is also dependent on increased BDNF signaling. Ketamine transiently increases BDNF translation in hippocampus, leading to enhanced synaptic plasticity and synaptic strength. Ketamine has been shown to increase BDNF translation by blocking NMDA receptor activity at rest, thereby inhibiting calcium influx and subsequently halting eukaryotic elongation factor 2 (eEF2) kinase leading to a desuppression of protein translation, including BDNF translation. The antidepressant-like response of ketamine is abolished in BDNF and TrkB conditional knockout mice, eEF2 kinase knockout mice, in mice carrying the BDNF met/met allele, and by intra-cortical infusions of BDNF-neutralizing antibodies. In summary, current data suggests that conventional antidepressants and ketamine mediate their antidepressant-like effects by increasing BDNF in forebrain regions, in particular the hippocampus, making BDNF an

  6. Association of cerebral metabolic activity changes with vagus nerve stimulation antidepressant response in treatment-resistant depression

    PubMed Central

    Conway, Charles R.; Chibnall, John T.; Gebara, Marie Anne; Price, Joseph L.; Snyder, Abraham Z.; Mintun, Mark A.; (Bud) Craig, A.D.; Cornell, Martha E.; Perantie, Dana C.; Giuffra, Luis A.; Bucholz, Richard D.; Sheline, Yvette I.

    2014-01-01

    Background Vagus nerve stimulation (VNS) has antidepressant effects in treatment resistant major depression (TRMD); these effects are poorly understood. This trial examines associations of subacute (3 months) and chronic (12 months) VNS with cerebral metabolism in TRMD. Objective 17Fluorodeoxyglucose positron emission tomography was used to examine associations between 12-month antidepressant VNS response and cerebral metabolic rate for glucose (CMRGlu) changes at 3 and 12 months. Methods Thirteen TRMD patients received 12 months of VNS. Depression assessments (Hamilton Depression Rating Scale [HDRS]) and PET scans were obtained at baseline (pre-VNS) and 3/12 months. CMRGlu was assessed in eight a priori selected brain regions (bilateral anterior insular [AIC], orbitofrontal [OFC], dorsolateral prefrontal [DLPFC], and anterior cingulate cortices [ACC]). Regional CMRGlu changes over time were studied in VNS responders (decreased 12 month HDRS by ≥50%) and nonresponders. Results A significant trend (decreased 3 month CMRGlu) in the right DLPFC was observed over time in VNS responders (n = 9; P = 0.006). An exploratory whole brain analysis (Puncorrected = 0.005) demonstrated decreased 3 month right rostral cingulate and DLPFC CMRGlu, and increased 12 month left ventral tegmental CMRGlu in responders. Conclusions/Limitations VNS response may involve gradual (months in duration) brain adaptations. Early on, this process may involve decreased right-sided DLPFC/cingulate cortical activity; longer term effects (12 months) may lead to brainstem dopaminergic activation. Study limitations included: a) a small VNS nonresponders sample (N = 4), which limited conclusions about nonresponder CMRGlu changes; b) no control group; and, c) patients maintained their psychotropic medications. PMID:23485649

  7. Use of antidepressant serotoninergic medications and cardiac valvulopathy: a nested case–control study in the health improvement network (THIN) database

    PubMed Central

    Lapi, Francesco; Nicotra, Federica; Scotti, Lorenza; Vannacci, Alfredo; Thompson, Mary; Pieri, Francesco; Mugelli, Niccolò; Zambon, Antonella; Corrao, Giovanni; Mugelli, Alessandro; Rubino, Annalisa

    2012-01-01

    AIMS To quantify the risk of cardiac valvulopathy (CV) associated with the use of antidepressant serotoninergic medications (SMs). METHODS We conducted a case–control study nested in a cohort of users of antidepressant SMs selected from The Health Improvement Network database. Patients who experienced a CV event during follow-up were cases. Cases were ascertained in a random sample of them. Up to 10 controls were matched to each case by sex, age, month and year of the study entry. Use of antidepressant SMs during follow-up was defined as current (the last prescription for antidepressant SMs occurred in the 2 months before the CV event), recent (in the 2–12 months before the CV event) and past (>12 months before the CV event). We fitted a conditional regression model to estimate the association between use of antidepressant SMs and the risk of CV by means of odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Sensitivity analyses were conducted to test the robustness of our results. RESULTS The study cohort included 752 945 subjects aged 18–89 years. Throughout follow-up, 1663 cases (incidence rate: 3.4 per 10 000 person-years) of CV were detected and were matched to 16 566 controls. The adjusted OR (95% CI) for current and recent users compared with past users of antidepressant SMs were 1.16 (0.96–1.40) and 1.06 (0.93–1.22), respectively. Consistent effect estimates were obtained when considering cumulative exposure to antidepressant SMs during follow-up. CONCLUSIONS These results would suggest that exposure to antidepressant SMs is not associated with an increased risk of CV. PMID:22356433

  8. The effects of antidepressants and pilocarpine on rat parotid glands: an immunohistochemical study

    PubMed Central

    Mattioli, Tatiana Maria Folador; da Silva, Silvana; Grégio, Ana Maria Trindade; Machado, Maria Ângela Naval; de Lima, Antônio Adilson Soares; Azevedo-Alanis, Luciana Reis

    2011-01-01

    OBJECTIVES: To evaluate the effects of antidepressants and pilocarpine on the quantity of myoepithelial cells and on the proliferation index of the epithelial cells of rat parotid glands. INTRODUCTION: Hyposalivation, xerostomia, and alterations in saliva composition are important clinical side effects related to the use of antidepressants. METHODS: Ninety male Wistar rats were allocated to nine groups. The control groups received saline for 30 (group C30) or 60 days (group C60) or pilocarpine for 60 days (group Pilo). The experimental groups were administered fluoxetine (group F30) or venlafaxine for 30 days (group V30); fluoxetine (group FS60) or venlafaxine (group VS60) with saline for 60 days; or fluoxetine (group FP60) or venlafaxine (group VP60) with pilocarpine for 60 days. Parotid gland specimens were processed, and the immunohistochemical expression of calponin and proliferating cell nuclear anti-antigen on the myoepithelial and parenchymal cells, respectively, was evaluated. Analysis of variance (ANOVA), Tukey HSD and Games-Howell tests were applied to detect differences among groups (p<0.05). RESULTS: Compared with the controls, chronic exposure to antidepressants was associated with an increase in the number of positively stained cells for calponin. In addition, venlafaxine administration for 30 days was associated with an increase in the number of positively stained cells for proliferating cell nuclear anti-antigen. Fluoxetine and pilocarpine (group FP60) induced a significant decrease in the number of positively stained cells for calponin compared with all other groups. CONCLUSIONS: The number of positively stained cells for calponin increased after chronic administration of antidepressants. The proliferation index of the epithelial cells of rat parotid glands was not altered by the use of antidepressants for 60 days. PMID:22179167

  9. Depression, Comorbidities, and Prescriptions of Antidepressants in a German Network of GPs and Specialists with Subspecialisation in Anthroposophic Medicine: A Longitudinal Observational Study

    PubMed Central

    Jeschke, Elke; Vollmar, Horst C.; Tabali, Manuela; Matthes, Harald

    2012-01-01

    Background. Depression is a major reason for counselling in primary care. Our study aims at evaluating pharmacological treatment strategies among physicians specialised in anthroposophic medicine (AM). Methods. From 2004 to 2008, twenty-two German primary care AM-physicians participated in this prospective, multicentre observational study. Multiple logistic regression was used to determine factors associated with a prescription of any antidepressant medication. Results. A total of 2444 patients with depression were included (mean age: 49.1 years (SD: 15.4); 77.3% female). 2645 prescriptions of antidepressants for 833 patients were reported. Phytotherapeutic preparations from Hypericum perforatum were the most frequently prescribed antidepressants over all (44.6% of all antidepressants), followed by amitriptyline (16.1%). The likelihood of receiving an antidepressant medication did not depend on comorbidity after controlling for age, gender, physician specialisation, and type of depression (adjusted OR (AOR) = 1.01; CI: 0.81–1.26). Patients who had cancer were significantly less likely to be prescribed an antidepressant medication than those who had no cancer (AOR = 0.75; CI: 0.57–0.97). Conclusion. This study provides a comprehensive analysis of everyday practice for the treatment of depression in AM -physicians. Further analysis regarding the occurrence of critical combinations is of high interest to health services research. PMID:23304204

  10. Depression, Comorbidities, and Prescriptions of Antidepressants in a German Network of GPs and Specialists with Subspecialisation in Anthroposophic Medicine: A Longitudinal Observational Study.

    PubMed

    Jeschke, Elke; Ostermann, Thomas; Vollmar, Horst C; Tabali, Manuela; Matthes, Harald

    2012-01-01

    Background. Depression is a major reason for counselling in primary care. Our study aims at evaluating pharmacological treatment strategies among physicians specialised in anthroposophic medicine (AM). Methods. From 2004 to 2008, twenty-two German primary care AM-physicians participated in this prospective, multicentre observational study. Multiple logistic regression was used to determine factors associated with a prescription of any antidepressant medication. Results. A total of 2444 patients with depression were included (mean age: 49.1 years (SD: 15.4); 77.3% female). 2645 prescriptions of antidepressants for 833 patients were reported. Phytotherapeutic preparations from Hypericum perforatum were the most frequently prescribed antidepressants over all (44.6% of all antidepressants), followed by amitriptyline (16.1%). The likelihood of receiving an antidepressant medication did not depend on comorbidity after controlling for age, gender, physician specialisation, and type of depression (adjusted OR (AOR) = 1.01; CI: 0.81-1.26). Patients who had cancer were significantly less likely to be prescribed an antidepressant medication than those who had no cancer (AOR = 0.75; CI: 0.57-0.97). Conclusion. This study provides a comprehensive analysis of everyday practice for the treatment of depression in AM -physicians. Further analysis regarding the occurrence of critical combinations is of high interest to health services research.

  11. Common genetic variation and antidepressant efficacy in major depressive disorder: a meta-analysis of three genome-wide pharmacogenetic studies.

    PubMed

    2013-02-01

    Indirect evidence suggests that common genetic variation contributes to individual differences in antidepressant efficacy among individuals with major depressive disorder, but previous studies may have been underpowered to detect these effects. A meta-analysis was performed on data from three genome-wide pharmacogenetic studies (the Genome-Based Therapeutic Drugs for Depression [GENDEP] project, the Munich Antidepressant Response Signature [MARS] project, and the Sequenced Treatment Alternatives to Relieve Depression [STAR*D] study), which included 2,256 individuals of Northern European descent with major depressive disorder, and antidepressant treatment outcomes were prospectively collected. After imputation, 1.2 million single-nucleotide polymorphisms were tested, capturing common variation for association with symptomatic improvement and remission after up to 12 weeks of antidepressant treatment. No individual association met a genome-wide threshold for statistical significance in the primary analyses. A polygenic score derived from a meta-analysis of GENDEP and MARS participants accounted for up to approximately 1.2% of the variance in outcomes in STAR*D, suggesting a weakly concordant signal distributed over many polymorphisms. An analysis restricted to 1,354 individuals treated with citalopram (STAR*D) or escitalopram (GENDEP) identified an intergenic region on chromosome 5 associated with early improvement after 2 weeks of treatment. Despite increased statistical power accorded by meta-analysis, the authors identified no reliable predictors of antidepressant treatment outcome, although they did identify modest, direct evidence that common genetic variation contributes to individual differences in antidepressant response.

  12. Examining non-response bias in substance use research--are late respondents proxies for non-respondents?

    PubMed

    Studer, Joseph; Baggio, Stéphanie; Mohler-Kuo, Meichun; Dermota, Petra; Gaume, Jacques; Bertholet, Nicolas; Daeppen, Jean-Bernard; Gmel, Gerhard

    2013-09-01

    Non-response is a major concern among substance use epidemiologists. When differences exist between respondents and non-respondents, survey estimates may be biased. Therefore, researchers have developed time-consuming strategies to convert non-respondents to respondents. The present study examines whether late respondents (converted former non-participants) differ from early respondents, non-consenters or silent refusers (consent givers but non-participants) in a cohort study, and whether non-response bias can be reduced by converting former non-respondents. 6099 French- and 5720 German-speaking Swiss 20-year-old males (more than 94% of the source population) completed a short questionnaire on substance use outcomes and socio-demographics, independent of any further participation in a cohort study. Early respondents were those participating in the cohort study after standard recruitment procedures. Late respondents were non-respondents that were converted through individual encouraging telephone contact. Early respondents, non-consenters and silent refusers were compared to late respondents using logistic regressions. Relative non-response biases for early respondents only, for respondents only (early and late) and for consenters (respondents and silent refusers) were also computed. Late respondents showed generally higher patterns of substance use than did early respondents, but lower patterns than did non-consenters and silent refusers. Converting initial non-respondents to respondents reduced the non-response bias, which might be further reduced if silent refusers were converted to respondents. Efforts to convert refusers are effective in reducing non-response bias. However, converted late respondents cannot be seen as proxies of non-respondents, and are at best only indicative of existing response bias due to persistent non-respondents. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  13. The association of antidepressant treatment with COPD maintenance medication use and adherence in a comorbid Medicare population: A longitudinal cohort study.

    PubMed

    Wei, Yu-Jung; Simoni-Wastila, Linda; Albrecht, Jennifer S; Huang, Ting-Ying; Moyo, Patience; Khokhar, Bilal; Harris, Ilene; Langenberg, Patricia; Netzer, Giora; Lehmann, Susan W

    2017-08-22

    The effect of treating comorbid depression to achieve optimal management of chronic obstructive pulmonary disease (COPD) has not yet empirically tested. We examined the association between antidepressant treatment and use of and adherence to COPD maintenance medications among patients with new-onset COPD and comorbid depression. Using 2006-2012 Medicare data, this retrospective cohort study identified patients with newly diagnosed COPD and new-onset major depression. Two exposures-antidepressant use (versus non-use) and adherence measured by proportion of days covered (PDC) (PDC ≥0.8 versus <0.8)-were assessed quarterly. We used marginal structural models to estimate the effects of prior antidepressant use and adherence on subsequent COPD maintenance inhaler use and adherence outcomes, accounting for time-varying confounders. A total of 25 458 COPD-depression patients, 82% with antidepressant treatment, were followed for a median of 2.5 years. Nearly half (48%) used at least 1 COPD maintenance inhaler in any given quarter; among users, 3 in 5 (61%) had a PDC of <0.8. Compared to patients with no antidepressant treatment, those with antidepressant use were more likely to use (relative ratio [RR] = 1.15, 95% confidence interval [CI] = 1.12- 1.17) and adhere to (RR = 1.08, 95% = 1.03-1.14) their COPD maintenance inhalers. Patients who adhered to antidepressant treatment were more likely to use and adhere to COPD maintenance inhalers. Regularly treated depression may increase use of and adherence to necessary maintenance medications for COPD. Antidepressant treatment may be a key determinant to improving medication-taking behaviors among COPD patients comorbid with depression. Copyright © 2017 John Wiley & Sons, Ltd.

  14. Effects of depression and antidepressant medications on hip fracture: A population-based cohort study in Taiwan.

    PubMed

    Cheng, Bi-Hua; Chen, Pau-Chung; Yang, Yao-Hsu; Lee, Chuan-Pin; Huang, Ko-En; Chen, Vincent C

    2016-09-01

    This study was conducted to investigate the effects of depression and antidepressant medications on hip fracture. The database of the Taiwan National Health Insurance with medical records of more than 1,000,000 individuals was searched for patients who had hip fracture with or without depression from 1998 to 2009. Patients with the following conditions were excluded: hip fracture due to cancer or traffic accidents, hip fracture that occurred before the diagnosis of depression, and use of antidepressants before the diagnosis of depression. A matched cohort of 139,110 patients was investigated, including 27,822 (17,309 females; 10,513 males) with depression and 111,288 (69,236 females; 42,052 males) without depression (1:4 randomly matched with age, sex, and index date). Among these patients, 232 (158 females and 74 males) had both hip fracture and depression, and 690 (473 females and 217 males) had hip fracture only. The Cox proportional-hazards regression method was used to determine the effect of depression on hip fracture. The hazard ratio (HR) for each clinical parameter was calculated after adjusting for confounders including sex, age, Charlson comorbidity index, urbanization, osteoporosis, and antidepressants. Results showed that patients with major depressive disorder had a 61% higher incidence of hip fracture than those without depression (HR 1.61, 95% confidence interval [CI] 1.19-2.18, P = 0.002). The risk of hip fracture for patients with less severe depressive disorder (dysthymia or depressive disorder, not otherwise specified) was not statistically higher than that of patients with no depression (HR 1.10, 95% CI = 0.91-1.34, P = 0.327). Among the patients with depression, females had a 49% higher incidence for hip fracture than males (HR 1.49, 95% CI 1.30-1.72, P < 0.001). The incidence of hip fracture also increased with age and Charlson comorbidity index scores. Analyses of both all (139,110) patients and only patients (27,822) with depression

  15. The Proton Pump Inhibitor Non-Responder: A Clinical Conundrum

    PubMed Central

    Hussain, Zilla H; Henderson, Emily E; Maradey-Romerao, Carla; George, Nina; Fass, Ronnie; Lacy, Brian E

    2015-01-01

    Gastroesophageal reflux disease (GERD) is a highly prevalent chronic condition where in stomach contents reflux into the esophagus causing symptoms, esophageal injury, and subsequent complications. Proton pump inhibitors (PPI) remain the mainstay of therapy for acid suppression. Despite their efficacy, significant proportions of GERD patients are either partial or non-responders to PPI therapy. Patients should be assessed for mechanisms that can lead to PPI failure and may require further evaluation to investigate for alternative causes. This monograph will outline a diagnostic approach to the PPI non-responder, review mechanisms associated with PPI failure, and discuss therapeutic options for those who fail to respond to PPI therapy. PMID:26270485

  16. Community-acquired pneumonia: identification and evaluation of nonresponders

    PubMed Central

    Conceição, Catarina; Póvoa, Pedro

    2013-01-01

    Community acquired pneumonia (CAP) is a relevant public health problem, constituting an important cause of morbidity and mortality. It accounts for a significant number of adult hospital admissions and a large number of those patients ultimately die, especially the population who needed mechanical ventilation or vasopressor support. Thus, early identification of CAP patients and its rapid and appropriate treatment are important features with impact on hospital resource consumption and overall mortality. Although CAP diagnosis may sometimes be straightforward, the diagnostic criteria commonly used are highly sensitive but largely unspecific. Biomarkers and microbiological documentation may be useful but have important limitations. Evaluation of clinical response is also critical especially to identify patients who fail to respond to initial treatment since these patients have a high risk of in-hospital death. However, the criteria of definition of non-response in CAP are largely empirical and frequently markedly diverse between different studies. In this review, we aim to identify criteria defining nonresponse in CAP and the pitfalls associated with this diagnosis. We also aim to overview the main causes of treatment failure especially in severe CAP and the possible strategies to identify and reassess non-responders trying to change the dismal prognosis associated with this condition. PMID:25165541

  17. Antidepressant use and work-related injuries.

    PubMed

    Kouvonen, A; Vahtera, J; Pentti, J; Korhonen, M J; Oksanen, T; Salo, P; Virtanen, M; Kivimäki, M

    2016-05-01

    Adverse effects of antidepressants are most common at the beginning of the treatment, but possible also later. We examined the association between antidepressant use and work-related injuries taking into account the duration of antidepressant use. Antidepressant use and work-related injuries between 2000 and 2011 were measured among 66 238 employees (mean age 43.8 years, 80% female) using linkage to national records (the Finnish Public Sector study). We analysed data using time-dependent modelling with individuals as their own controls (self-controlled case-series design). In 2238 individuals who had used antidepressants and had a work-related injury during a mean follow-up of 7.8 years, no increase in the risk of injury was observed in the beginning of antidepressant treatment. However, an increased injury risk was seen after 3 months of treatment (rate ratio, compared with no recent antidepressant use, 1.27, 95% confidence interval 1.10-1.48). This was also the case among those who had used only selective serotonin reuptake inhibitors (n = 714; rate ratio 1.41, 95% confidence interval 1.08-1.83). Antidepressant use was not associated with an increased risk of work-related injury at the beginning of treatment. Post-hoc analyses of antidepressant trials are needed to determine whether long-term use of antidepressants increases the risk of work-related injury.

  18. Protocol for the THREAD (THREshold for AntiDepressants) study: a randomised controlled trial to determine the clinical and cost-effectiveness of antidepressants plus supportive care, versus supportive care alone, for mild to moderate depression in UK general practice

    PubMed Central

    Chatwin, Judy; Kendrick, Tony

    2007-01-01

    Background Depression guidelines in the UK recommended a policy of watchful waiting for mild depression due to a lack of evidence for the effectiveness of antidepressant treatment for mild cases. However there has been relatively little research carried out in primary care to help establish the severity threshold at which antidepressant treatment is effective and cost-effective. Methods/Design The THREAD (THREshold for AntiDepressants) study is a multi-centre randomised controlled trial designed to determine the clinical and cost effectiveness of a selective serotonin reuptake inhibitor (SSRI) plus general practitioner (GP) supportive care, versus supportive care alone, for mild to moderate depression in primary care. The aim is to recruit 300 patients from three centres (Southampton, London and Liverpool). Depressive symptoms will be assessed at baseline, 12 weeks and 26 weeks, using the 17-item Hamilton Depression Rating Scale (HDRS). Two severity sub-groups of patients will be recruited, with HDRS scores of 12–15, and 16–19. Possible predictors of response will be explored including life events and difficulties and alcohol consumption. Analysis of covariance, controlling for baseline value, severity group and centre will be used to estimate the overall treatment effectiveness (difference in HDRS score) at final follow up. The primary analysis will be by 'intention to treat' using double sided tests. The interaction between severity sub-group and treatment will be tested, and if appropriate, effects within separate severity sub-groups estimated. The economic analysis will compare the two treatment groups in terms of mean costs and cost-effectiveness. Discussion The results of this study will give GPs important information to help them determine the severity of depression at which antidepressant treatment is likely to be cost-effective. PMID:17204136

  19. Milnacipran: a unique antidepressant?

    PubMed

    Kasper, Siegfried; Pail, Gerald

    2010-09-07

    Tricyclic antidepressants (TCAs) are among the most effective antidepressants available, although their poor tolerance at usual recommended doses and toxicity in overdose make them difficult to use. While selective serotonin reuptake inhibitors (SSRIs) are better tolerated than TCAs, they have their own specific problems, such as the aggravation of sexual dysfunction, interaction with coadministered drugs, and for many, a discontinuation syndrome. In addition, some of them appear to be less effective than TCAs in more severely depressed patients. Increasing evidence of the importance of norepinephrine in the etiology of depression has led to the development of a new generation of antidepressants, the serotonin and norepinephrine reuptake inhibitors (SNRIs). Milnacipran, one of the pioneer SNRIs, was designed from theoretic considerations to be more effective than SSRIs and better tolerated than TCAs, and with a simple pharmacokinetic profile. Milnacipran has the most balanced potency ratio for reuptake inhibition of the two neurotransmitters compared with other SNRIs (1:1.6 for milnacipran, 1:10 for duloxetine, and 1:30 for venlafaxine), and in some studies milnacipran has been shown to inhibit norepinephrine uptake with greater potency than serotonin (2.2:1). Clinical studies have shown that milnacipran has efficacy comparable with the TCAs and is superior to SSRIs in severe depression. In addition, milnacipran is well tolerated, with a low potential for pharmacokinetic drug-drug interactions. Milnacipran is a first-line therapy suitable for most depressed patients. It is frequently successful when other treatments fail for reasons of efficacy or tolerability.

  20. Cognitive Therapy Alone and in Combination with Antidepressants for Anxious Depression: A STAR*D Report

    PubMed Central

    Farabaugh, Amy; Alpert, Jonathan; Wisniewski, Stephen R.; Otto, Michael W.; Fava, Maurizio; Baer, Lee; Perlis, Roy; Friedman, Edward S.; Nyer, Maren; Bitran, Stella; Balasubramani, G.K.; Inamori, Aya; Trivedi, Madhukar; Thase, Michael

    2012-01-01

    Background Anxious depression, defined as MDD with high levels of anxiety, has been associated with lower rates of antidepressant response and remission as well as greater chronicity, suicidality and antidepressant side-effect burden. The primary aim of this study was to assess the effectiveness of cognitive therapy (CT) alone or in combination with medications for anxious versus non-anxious depression. Methods We assessed the STAR*D study participants who were partial or non-responders to citalopram. Subjects were then either switched (n = 696) to a new antidepressant or to CT alone, or they were kept on citalopram and augmented (n = 577) with another antidepressant or CT. We compared response and remission rates of those who met criteria for anxious depression to those who did not across treatment conditions. Results Those with anxious depression had significantly lower remission rates based on the QIDS, whether assigned to switch or augmentation, compared to those with non-anxious depression. Those with anxious depression, compared to those without, had significantly lower response rates based on the QIDS only in the switch group. There was no significant interaction between anxious depression and treatment assignment. Limitations Limitations include the use of citalopram as the only Level 1 pharmacotherapy and medication augmentation option, depression-focused CT rather than anxiety-focused CT, and focus on acute treatment outcomes. Conclusions Individuals with anxious depression appear to experience higher risk of poorer outcome following pharmacotherapy and/or CT after an initial course of SSRI, and continued efforts to target this challenging form of depression are needed. PMID:22877961

  1. Long-Term Echocardiographic Response to Cardiac Resynchronization Therapy in Initial Nonresponders.

    PubMed

    Burns, Kevin V; Gage, Ryan M; Curtin, Antonia E; Bank, Alan J

    2015-12-01

    The aim of this study was to investigate the frequency and clinical implications of a delayed echocardiographic response to cardiac resynchronization therapy (CRT). Long-term prognosis for CRT patients is routinely based on the assessment of echocardiograms after 6 to 12 months of therapy. Some patients, however, may require a longer period of therapy before echocardiographic improvements are detectable. This observational study included all patients with heart failure (HF) receiving a CRT device at a single center from 2003 to 2011. Eligible patients met current indications and had technically adequate echocardiograms from before implantation, approximately 1 year after implantation (mid-term), and ≥3 years after implantation (long-term). A positive echocardiographic response to CRT was defined as a reduction in left ventricular end-systolic volume ≥15%. All-cause mortality was compared for patients in 3 response groups: mid-term responders, long-term responders, and nonresponders. During this study, 294 patients met the study criteria. Of the 120 patients who were nonresponders after 1 year, 52 (43%) experienced a delayed positive response. Delayed, long-term responders had mortality and hospitalization rates similar to mid-term responders and significantly lower than nonresponders. Among patients surviving at least 3 years after implantation of a CRT device and with echocardiographic follow-up, a significant portion of nonresponders after 1 year of CRT experience a delayed echocardiographic response after a longer period of time. Survival and hospitalization rates were similar for all echocardiographic responders, regardless of the time at which the response occurred. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  2. Prenatal Antidepressants and Autism Spectrum Disorder

    DTIC Science & Technology

    2014-09-01

    1 AWARD NUMBER: W81XWH-13-1-0306 TITLE: Prenatal Antidepressants and Autism Spectrum Disorder PRINCIPAL INVESTIGATOR...TYPE Annual 3. DATES COVERED 1Sept 2013-31Aug2014 4. TITLE AND SUBTITLE Prenatal Antidepressants and Autism Spectrum Disorder 5a... antidepressants (ADs) during pregnancy. We are testing this hypothesis in rodents. The study is a 2-year long experiment to be decoded and

  3. Ghrelin Serum Concentrations Are Associated with Treatment Response During Lithium Augmentation of Antidepressants

    PubMed Central

    Bopp, Sandra; Schlattmann, Peter; Himmerich, Hubertus; Bschor, Tom; Richter, Christoph; Elstner, Samuel; Stamm, Thomas J; Schulz-Ratei, Brigitte; Lingesleben, Alexandra; Reischies, Friedel M; Sterzer, Philipp; Borgwardt, Stefan; Bauer, Michael; Heinz, Andreas; Hellweg, Rainer; Lang, Undine E; Adli, Mazda

    2017-01-01

    Abstract Background Lithium augmentation of antidepressants is an effective strategy in treatment-resistant depression. The proteohormone ghrelin is thought to be involved in the pathophysiology of depression. The purpose of this study was to investigate the association of treatment response with the course of ghrelin levels during lithium augmentation. Method Ghrelin serum concentrations and severity of depression were measured in 85 acute depressive patients before and after 4 weeks of lithium augmentation. Results In a linear mixed model analysis, we found a significant effect of response*time interaction (F1.81=9.48; P=.0028): under treatment, ghrelin levels increased in nonresponders and slightly decreased in responders to lithium augmentation. The covariate female gender had a significant positive effect (F1.83=4.69; P=.033), whereas time, response, appetite, and body mass index (kg/m2) did not show any significant effect on ghrelin levels (P>.05). Conclusion This is the first study showing that the course of ghrelin levels separates responders and nonresponders to lithium augmentation. Present results support the hypothesis that ghrelin serum concentrations might be involved in response to pharmacological treatment of depression.

  4. Cardiovascular disease and death associated with depression and antidepressants in the Melbourne Longitudinal Studies on Healthy Ageing (MELSHA).

    PubMed

    Atlantis, Evan; Grayson, Dave A; Browning, Colette; Sims, Jane; Kendig, Hal

    2011-04-01

    Cardiovascular disease (CVD) and death may be associated with depression and antidepressants, but published findings remain equivocal. The authors aimed to determine the risk of CVD incidence and death associated with several classifications of depression. A prospective cohort study was conducted (1994-2006) in a regionally representative sample of 1000 non-institutionalised older Australians age 65+ years (47% men). Endpoints were non-fatal CVD incidence and death over 10 and 12-years, respectively. Depression incidence was assessed at 2-years. Depression related predictors were defined by symptoms (Psychogeriatric Assessment Scales, depression scale) and/or antidepressants to determine independent and/or joint effects on endpoints. Cox regressions determined unadjusted and multiple-adjusted (for significant covariates) hazard ratios (HR). Baseline response rate was 70.3%. Aggregate dropout rate was approximately 24% for survivors at biennial follow-ups, but death status was ascertained for all participants. Several classifications of depression predicted death in unadjusted analyses (39-60% >1), but effects disappeared in multiple-adjusted analyses (in which all HRs became <1 and non-significant). Depression related predictors were thus not associated with CVD incidence; or death after accounting for confounding mostly by CVD, diabetes and poor functional health covariates. Prevalent arthritis, respiratory disease and daily pain were predictors (P < 0.05) of depression incidence. Depression related predictors were not independently associated with CVD incidence or death in older people. Antidepressants were not associated with CVD or premature death, accounting for whether participants' remained symptomatic or not. Depression co-occurs with and might be partly caused by chronic disease and poor functional health. Copyright © 2010 John Wiley & Sons, Ltd.

  5. Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study.

    PubMed

    Sanches, Rafael Faria; de Lima Osório, Flávia; Dos Santos, Rafael G; Macedo, Ligia R H; Maia-de-Oliveira, João Paulo; Wichert-Ana, Lauro; de Araujo, Draulio Barros; Riba, Jordi; Crippa, José Alexandre S; Hallak, Jaime E C

    2016-02-01

    Ayahuasca is an Amazonian botanical hallucinogenic brew which contains dimethyltryptamine, a 5-HT2A receptor agonist, and harmine, a monoamine-oxidase A inhibitor. Our group recently reported that ayahuasca administration was associated with fast-acting antidepressive effects in 6 depressive patients. The objective of the present work was to assess the antidepressive potentials of ayahuasca in a bigger sample and to investigate its effects on regional cerebral blood flow. In an open-label trial conducted in an inpatient psychiatric unit, 17 patients with recurrent depression received an oral dose of ayahuasca (2.2 mL/kg) and were evaluated with the Hamilton Rating Scale for Depression, the Montgomery-Åsberg Depression Rating Scale, the Brief Psychiatric Rating Scale, the Young Mania Rating Scale, and the Clinician Administered Dissociative States Scale during acute ayahuasca effects and 1, 7, 14, and 21 days after drug intake. Blood perfusion was assessed eight hours after drug administration by means of single photon emission tomography. Ayahuasca administration was associated with increased psychoactivity (Clinician Administered Dissociative States Scale) and significant score decreases in depression-related scales (Hamilton Rating Scale for Depression, Montgomery-Åsberg Depression Rating Scale, Brief Psychiatric Rating Scale) from 80 minutes to day 21. Increased blood perfusion in the left nucleus accumbens, right insula and left subgenual area, brain regions implicated in the regulation of mood and emotions, were observed after ayahuasca intake. Ayahuasca was well tolerated. Vomiting was the only adverse effect recorded, being reported by 47% of the volunteers. Our results suggest that ayahuasca may have fast-acting and sustained antidepressive properties. These results should be replicated in randomized, double-blind, placebo-controlled trials.

  6. The association between use of serotonergic antidepressants and perioperative bleeding during total hip arthroplasty--a cohort study.

    PubMed

    Dall, Michael; Primdahl, Annie; Damborg, Frank; Nymark, Tine; Hallas, Jesper

    2014-09-01

    In vitro studies have shown that selective serotonin reuptake inhibitors inhibit platelet aggregation. It is well documented that SSRIs cause serious gastrointestinal bleeding, but studies on other bleeding manifestations have been equivocal. Our objective was to determine a possible association between use of serotonergic antidepressants (SA) and perioperative bleeding during hip replacements. We conducted a retrospective study between 1 January 2007 and 30 June 2012 among patients that underwent a primary unilateral uncemented total hip arthroplasty (THA). Information was collected on the observed blood loss and the need for blood transfusions among this group. We compared the blood loss between users of SA, users of non-serotonergic antidepressants (NSA) and non-users, while adjusting for potential confounders using multivariate linear regression. We indentified 1318 patients that underwent a THA in the study period. The average volume of surgical bleeding was 350 ml. The adjusted incremental blood loss associated with use of SA and NSA was 93, 95% confidence interval (38-147) ml and -50 (-125 to 25) ml compared with non-use. Only 48 subjects (3.6%) had transfusions. Use of SA was associated with an increased blood loss compared with non-users. The hypothesis that SA impairs haemostasis is supported by these results.

  7. Antidepressants and Alcohol

    MedlinePlus

    ... depressive disorder) Why is it bad to mix antidepressants and alcohol? Answers from Daniel K. Hall-Flavin, M.D. It's best to avoid combining antidepressants and alcohol. It may worsen your symptoms, and ...

  8. Poor response to antidepressant medication of patients with depression accompanied by somatic symptomatology in the STAR*D Study.

    PubMed

    Silverstein, Brett; Patel, Priya

    2011-05-15

    Studies suggest that the gender difference in the prevalence of depression results because women exhibit higher prevalence than men of a depressive phenotype associated with somatic symptoms. Because this phenotype has been found to be based in psychosocial forces, it may not respond well to antidepressant medication. In this study, data from the STAR*D Study were analyzed to compare remission rates in response to an SSRI and to several other antidepressants of patients exhibiting depression accompanied by somatic symptomatology versus other patients. Scores on the Clinician Rated Quick Inventory of Depressive Symptomatology were used to measure clinical remission in response to medication. Patients exhibiting depression accompanied by somatic symptomatology exhibited less remission to the SSRI Citalopram (31% versus 43%) and to the various medications administered in level 3 (14% versus 25%) than did other patients in STAR*D. The low rates of remission in response to medication of patients exhibiting somatic symptomatology were not due to the greater proportion of women, nor to the greater proportion of patients exhibiting anxiety disorders, among patients exhibiting somatic symptomatology. Remission rates were found to be related to exhibiting somatic symptomatology not to exhibiting nonsomatic symptoms. Copyright © 2010 Elsevier Ltd. All rights reserved.

  9. Does good leadership buffer effects of high emotional demands at work on risk of antidepressant treatment? A prospective study from two Nordic countries.

    PubMed

    Madsen, Ida E H; Hanson, Linda L Magnusson; Rugulies, Reiner; Theorell, Töres; Burr, Hermann; Diderichsen, Finn; Westerlund, Hugo

    2014-08-01

    Emotionally demanding work has been associated with increased risk of common mental disorders. Because emotional demands may not be preventable in certain occupations, the identification of workplace factors that can modify this association is vital. This article examines whether effects of emotional demands on antidepressant treatment, as an indicator of common mental disorders, are buffered by good leadership. We used data from two nationally representative work environment studies, the Danish Work Environment Cohort Study (n = 6,096) and the Swedish Longitudinal Occupational Survey of Health (n = 3,411), which were merged with national registers on antidepressant purchases. All individuals with poor self-reported baseline mental health or antidepressant purchases within 8.7 months before baseline were excluded, and data analysed prospectively. Using Cox regression, we examined hazard ratios (HRs) for antidepressants in relation to the joint effects of emotional demands and leadership quality. Buffering was assessed with Rothman's synergy index. Cohort-specific risk estimates were pooled by random effects meta-analysis. High emotional demands at work were associated with antidepressant treatment whether quality of leadership was poor (HR = 1.84, 95 % CI 1.32-2.57) or good (HR = 1.70, 95 % CI 1.25-2.31). The synergy index was 0.66 (95 % CI 0.34-1.28). Our findings suggest that good leadership does not substantially ameliorate any effects of emotional demands at work on employee mental health. Further research is needed to identify possible preventive measures for this work environment exposure.

  10. Absence of evidence for increase in risk for autism or attention-deficit hyperactivity disorder following antidepressant exposure during pregnancy: a replication study.

    PubMed

    Castro, V M; Kong, S W; Clements, C C; Brady, R; Kaimal, A J; Doyle, A E; Robinson, E B; Churchill, S E; Kohane, I S; Perlis, R H

    2016-01-05

    Multiple studies have examined the risk of prenatal antidepressant exposure and risk for autism spectrum disorder (ASD) or attention-deficit hyperactivity disorder (ADHD), with inconsistent results. Precisely estimating such risk, if any, is of great importance in light of the need to balance such risk with the benefit of depression and anxiety treatment. We developed a method to integrate data from multiple New England health systems, matching offspring and maternal health data in electronic health records to characterize diagnoses and medication exposure. Children with ASD or ADHD were matched 1:3 with children without neurodevelopmental disorders. Association between maternal antidepressant exposure and ASD or ADHD liability was examined using logistic regression, adjusting for potential sociodemographic and psychiatric confounding variables. In new cohorts of 1245 ASD cases and 1701 ADHD cases, along with age-, sex- and socioeconomic status matched controls, neither disorder was significantly associated with prenatal antidepressant exposure in crude or adjusted models (adjusted odds ratio 0.90, 95% confidence interval 0.50-1.54 for ASD; 0.97, 95% confidence interval 0.53-1.69 for ADHD). Pre-pregnancy antidepressant exposure significantly increased risk for both disorders. These results suggest that prior reports of association between prenatal antidepressant exposure and neurodevelopmental disease are likely to represent a false-positive finding, which may arise in part through confounding by indication. They further demonstrate the potential to integrate data across electronic health records studies spanning multiple health systems to enable efficient pharmacovigilance investigation.

  11. Pacemaker optimization in nonresponders to cardiac resynchronization therapy: left ventricular pacing as an available option.

    PubMed

    Gage, Ryan M; Burns, Kevin V; Vatterott, Daniel B; Kubo, Spencer H; Bank, Alan J

    2012-06-01

    Echocardiographic (ECHO)-guided pacemaker optimization (PMO) in cardiac resynchronization therapy (CRT) nonresponders acutely improves left ventricular (LV) function. However, the chronic results of LV pacing in this group are less understood. We retrospectively studied 28 CRT nonresponders optimized based on ECHO to LV pacing and compared them to 28 age- and gender-matched patients optimized to biventricular (BiV) pacing. ECHOs with tissue Doppler imaging assessed LV hemodynamics before, immediately after, and 29 ± 16 months after PMO. Also, 56 age- and gender-matched CRT responders were included for comparison of clinical outcomes. PMO resulted in acute improvements in longitudinal LV systolic function and several measures of dyssynchrony, with greater improvements in the LV paced group. Chronic improvements in ejection fraction (EF) (3.2 ± 7.7%), and left ventricle end-systolic volume (LVESV) (-11 ± 36 mL) and one dyssynchrony measure were seen in the combined group. Chronically, both LV and BiV paced patients improved some measures of systolic function and dyssynchrony although response varied between the groups. Survival at 3.5 years was similar (P = 0.973) between the PMO (58%) and nonoptimized groups (58%) but survival free of cardiovascular hospitalization was significantly (P = 0.037) better in the nonoptimized group. CRT nonresponders undergoing PMO to either LV or BiV pacing have acute improvements in longitudinal systolic function and some measures of dyssynchrony. Some benefits are sustained chronically, with improvements in EF, LVESV, and dyssynchrony. A strategy of ECHO-guided PMO results in survival for CRT nonresponders similar to that of CRT patients not referred for PMO. ©2012, The Authors. Journal compilation ©2012 Wiley Periodicals, Inc.

  12. Clinical outcomes following switch from venlafaxine ER to desvenlafaxine in nonresponders and responders.

    PubMed

    Guico-Pabia, C J; Jiang, Q; Ninan, P T; Thase, M E

    2011-09-01

    This post hoc analysis examined efficacy and tolerability of open-label desvenlafaxine in patients with major depressive disorder switched from blinded placebo, venlafaxine extended release (ER), or desvenlafaxine. Patients who completed 8 weeks of double-blind therapy with placebo (n = 176), venlafaxine ER (n = 175), or desvenlafaxine (n = 143) enrolled in a 10-month, open-label extension study and received desvenlafaxine 200 to 400 mg/d. Efficacy (17-item Hamilton Depression Rating Scale [HDRS(17)]) was assessed separately for nonresponders and responders to double-blind treatment. Tolerability during the first month of open-label desvenlafaxine was assessed. Among nonresponders (n = 134) to double-blind placebo, venlafaxine ER, and desvenlafaxine, mean decreases in HDRS(17) scores were -10.9, -7.3, and -7.7, respectively; HDRS(17) response rates were 67%, 53%, and 48%, respectively. Although responders (n = 360) to double-blind placebo, venlafaxine ER, and desvenlafaxine had more modest decreases on the HDRS(17), response rates were higher (84%, 87%, and 83%, respectively). Rates of adverse events were highest during week 1, and decreased afterward for the remainder of the first month of treatment. Among nonresponders to 8 weeks of double-blind venlafaxine ER, desvenlafaxine, or placebo, 48% to 67% subsequently responded to open-label desvenlafaxine. Over 80% of responders to double-blind therapy maintained response on open-label desvenlafaxine. The switch from venlafaxine ER to desvenlafaxine was well tolerated.

  13. Participation in a mail survey: role of repeated mailings and characteristics of nonrespondents among recent mothers.

    PubMed

    Larroque, B; Kaminski, M; Bouvier-Colle, M H; Hollebecque, V

    1999-04-01

    This study analysed the characteristics of respondent and nonrespondent mothers at each stage of a survey procedure, from a initial questionnaire to a reminder letter and two repeated mailings. Of 938 mothers of liveborn children who, while maternity inpatients, received a questionnaire and information about a mail survey to follow 2 months later, 828 completed and returned the initial questionnaire, 708 agreed to participate in the mail survey and were sent the mail questionnaire, and 612 finally completed and returned the questionnaire at 2 months. There were differences between respondents and non-respondents for socio-demographic factors at each stage of the process. The final response rate to the mail questionnaire was higher among mothers who were younger, were breast feeding, and had more education, an occupation and fewer children. The characteristics of late respondents were intermediate between those of early to middle respondents and nonrespondents for age, educational level, breast feeding and occupation. Maternal and infant health varied only slightly according to response status. Repeated mailings increased response and diminished selection. A mail questionnaire after contact in a maternity ward is a cost-effective means of gathering data about a large sample of recent mothers and their children.

  14. Potential antidepressant and resilience mechanism revealed by metabolomic study on peripheral blood mononuclear cells of stress resilient rats.

    PubMed

    Li, Juan; Zhang, Shu-Xiao; Wang, Wei; Cheng, Ke; Guo, Hua; Rao, Cheng-Long; Yang, De-Yu; He, Yong; Zou, De-Zhi; Han, Yu; Zhao, Li-Bo; Li, Peng-Fei; Xie, Peng

    2017-03-01

    Resilience is an active coping response to stress, which plays a very important role in major depressive disorder study. The molecular mechanisms underlying such resilience are poorly understood. Peripheral blood mononuclear cells (PBMCs) were promising objects in unveiling the underlying pathogenesis of resilience. Hereby we carried out successive study on PBMCs metabolomics in resilient rats of chronic unpredictable mild stress (CUMS) model. A gas chromatography-mass spectrometry (GC-MS) metabolomic approach coupled with principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) was used to detect differential metabolites in PBMCs of resilient rats. Ingenuity Pathways Analysis (IPA) was applied for pathway analysis. A set of differential metabolites including Malic acid, Ornithine, l-Lysine, Stigmasterol, Oleic acid, γ-Tocopherol, Adenosine and N-acetyl-d-glucosamine were significantly altered in resilient rats, meanwhile promoting antidepressant research. As revealed by IPA that aberrant energy metabolism, HIFα signaling, neurotransmitter, O-GlcNAcylation and cAMP signaling cascade in peripheral might be evolved in the pathogenesis of coping mechanism. The GC-MS based metabolomics may contribute to better understanding of resilience, as well as shedding light on antidepressant discovery. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Evidence for shortening the duration of clinical trials of antidepressants and a proposed paradigm for such studies.

    PubMed

    Katz, Martin M; Berman, Nancy; Bowden, Charles L; Frazer, Alan

    2015-06-01

    The model for the clinical trial of putative antidepressants is older than 50 years. Recent failures resulted in several drug companies, citing excessive costs of lengthy multiweek trials, abandoning new drug development. Collateral problems include patients being maintained on ineffective drugs for 6 to 8 weeks, increasing the pain associated with the disorder. This study proposes an alternative model for testing new drugs that both shortens the clinical trial and broadens its aims to include a profile of the new drug's specific clinical actions. This alternative model makes it possible to uncover the drug's application to treatment of other mental disorders. It is based on recent findings that onset of action and a large proportion of an effective drug's positive effects, contrary to early reports, occur within the first 2 weeks. It uses an index of the 2-week "early improvement" to predict a 6-week outcome. Measuring effects on the dimensions of the disorder determined that effective antidepressants act on mood and behavioral components and that the Hamilton and new "multivantaged" methods can provide a profile of specific drug actions distinguished from nonspecific placebo effects, at 2 weeks. This early improvement is predictive of positive outcome of 6-week trials. Because of the implications of successful 2-week trials for reducing costs, providing data on specific clinical drug actions, potentially stimulating new drug development, and reducing patient suffering from extended treatment with ineffective drugs, a large sample, prospective study designed in accord with this test trial is recommended.

  16. Distinctive pretreatment features of bilateral nucleus accumbens networks predict early response to antidepressants in major depressive disorder.

    PubMed

    Hou, Zhenghua; Gong, Liang; Zhi, Mengmeng; Yin, Yingying; Zhang, Yuqun; Xie, Chunming; Yuan, Yonggui

    2017-10-02

    The pretreatment neuroimaging markers from the resting-state brain network that could predict the early response to antidepressants are still unclear. The aim of the present study was to identify the performance of reward network features for discriminating patients with a dampened response to antidepressants. A total of 81 major depressive disorder (MDD) patients (44 patients with treatment-responsive depression (RD) and 37 patients with non-responding depression (NRD)) and 43 healthy controls (HC) underwent resting-state functional magnetic resonance imaging scans and clinical estimates. Bilateral nucleus accumbens (NAcc)-based networks were constructed for further functional connectivity (FC) analysis. The FC of the right superior frontal gyrus (SFG) (area under curve (AUC) = 0.837) and left parahippocampus (AUC = 0.770) within the left NAcc reward network, as well as the FC of the left SFG (AUC = 0.827) within the right NAcc reward network, could distinguish NRD subjects from RD subjects relatively well. Taken together, when considering the distinctive connectional pattern of the bilateral reward circuits, the synthetical differentiating effect was achieved to an optimal performance for discriminating NRD patients (AUC = 0.869), with balanced sensitivity (0.838) and specificity (0.818). The distinct pretreatment characteristics of the reward network make specific contributions to the early response to antidepressants and establish a promising imaging predictor for the classification of early efficacy.

  17. The male heart and the female mind: a study in the gendering of antidepressants and cardiovascular drugs in advertisements in Irish medical publication.

    PubMed

    Curry, Phillip; O'Brien, Marita

    2006-04-01

    Stereotypes which suggest that cardiovascular disease and depression are related to gender can have consequences for the mental and physical health outcomes of both men and women. This study examines how these stereotypes may be reinforced by medical publications advertising for cardiovascular and antidepressant medication. A random sample of 61 (with no repeats) advertisements which appeared in Irish medical publications between July 2001 and December 2002 were analysed using both content and semiotic analysis. Results indicate that the meanings created by advertisers for cardiovascular drugs and antidepressants did in fact gender these products. Women were depicted as the predominant users of antidepressants and men as the main users of cardiovascular drugs. The images used identified two stereotyped patients: the 'male' heart patient and the depressed 'female' patient. Furthermore, the imagery and language used to promote the two categories of medication tended to strengthen gendered associations.

  18. Effects of depression, anxiety, comorbidity, and antidepressants on resting-state heart rate and its variability: an ELSA-Brasil cohort baseline study.

    PubMed

    Kemp, Andrew H; Brunoni, Andre R; Santos, Itamar S; Nunes, Maria A; Dantas, Eduardo M; Carvalho de Figueiredo, Roberta; Pereira, Alexandre C; Ribeiro, Antonio L P; Mill, José G; Andreão, Rodrigo V; Thayer, Julian F; Benseñor, Isabela M; Lotufo, Paulo A

    2014-12-01

    Increases in resting-state heart rate and decreases in its variability are associated with substantial morbidity and mortality, yet contradictory findings have been reported for the effects of the mood and anxiety disorders and of antidepressants. The authors investigated heart rate and heart rate variability in a large cohort from Brazil, using propensity score weighting, a relatively novel method, to control for numerous potential confounders. A total of 15,105 participants were recruited in the Brazilian Longitudinal Study of Adult Health. Mood and anxiety disorders were ascertained using the Portuguese version of the Clinical Interview Schedule-Revised. Heart rate and its variability were extracted from 10-minute resting-state electrocardiograms. Regressions weighted by propensity scores were carried out to compare participants with and without depressive or anxiety disorders, as well as users and non-users of antidepressants, on heart rate and heart rate variability. Use of antidepressants was associated with increases in heart rate and decreases in its variability. Effects were most pronounced for the tricyclic antidepressants (Cohen's d, 0.72-0.81), followed by serotonin and norepinephrine reuptake inhibitors (Cohen's d, 0.42-0.95) and other antidepressants (Cohen's d, 0.37-0.40), relative to participants not on antidepressants. Only participants with generalized anxiety disorder showed robust, though small, increases in heart rate and decreases in its variability after propensity score weighting. The findings may, in part, underpin epidemiological findings of increased risk for cardiovascular morbidity and mortality. Many factors that have an adverse impact on cardiac activity were controlled for in this study, highlighting the importance of cardiovascular risk reduction strategies. Further study is needed to examine whether, how, and when such effects contribute to morbidity and mortality.

  19. Use of antidepressants near delivery and risk of postpartum hemorrhage: cohort study of low income women in the United States.

    PubMed

    Palmsten, Kristin; Hernández-Díaz, Sonia; Huybrechts, Krista F; Williams, Paige L; Michels, Karin B; Achtyes, Eric D; Mogun, Helen; Setoguchi, Soko

    2013-08-21

    To determine whether use of serotonin or non-serotonin reuptake inhibitors near to delivery is associated with postpartum hemorrhage. Cohort study. 2000-07 nationwide Medicaid data (Medicaid Analytic eXtract). 106,000 pregnant women aged 12-55 with a diagnosis of mood or anxiety disorder. Women were categorized into four mutually exclusive exposure groups according to pharmacy dispensing data: current (delivery date), recent (1-30 days before delivery date), past (1-5 months before delivery date), and no exposure (reference group). Risk of postpartum hemorrhage by timing of exposure and by serotonin or non-serotonin reuptake inhibitors, classes of antidepressant, and antidepressant types. Relative risks and 95% confidence intervals adjusted for delivery year, risk factors for postpartum hemorrhage, indicators of severity of mood/anxiety disorder, other indications for antidepressants, and other drugs. High dimensional propensity score (hdPS) methods were used to empirically identify and adjust for additional factors. 12,710 (12%) women had current exposure to serotonin reuptake inhibitor monotherapy, and 1495 (1.4%) women had current exposure to non-serotonin reuptake inhibitor monotherapy. The risk of postpartum hemorrhage was 2.8% among women with mood/anxiety disorders but no exposure to antidepressants, 4.0% in the current users of serotonin reuptake inhibitors, 3.8% in the current users of non-serotonin reuptake inhibitors, 3.2% in the recent users of serotonin reuptake inhibitors, 3.1% in the recent users of non-serotonin reuptake inhibitors, 2.5% in the past users of serotonin reuptake inhibitors, and 3.4% in the past users of non-serotonin reuptake inhibitors. Compared with no exposure, women with current exposure to serotonin reuptake inhibitors had a 1.47-fold increased risk of postpartum hemorrhage (95% confidence interval 1.33 to 1.62) and women with current non-serotonin reuptake inhibitor exposure had a 1.39-fold increased risk (1.07 to 1.81). Results

  20. Job insecurity and the use of antidepressant medication among Danish employees with and without a history of prolonged unemployment: a 3.5-year follow-up study.

    PubMed

    Rugulies, R; Thielen, K; Nygaard, E; Diderichsen, F

    2010-01-01

    A study was undertaken to investigate whether job insecurity predicts incident use of antidepressant medication and whether the association is modified by a history of prolonged unemployment. A prospective follow-up study was performed in 5142 Danish employees, including 632 employees with and 4510 without a history of prolonged unemployment. Participants were drawn from a random 10% sample of the Danish population. Survey data on job insecurity were linked with register data on history of unemployment and dispensing of antidepressant medication between June 2000 and December 2003 retrieved from the Danish Medicinal Product Statistics. Respondents with major depression at baseline or antidepressant use in the 5 years preceding baseline were excluded. Job insecurity predicted use of antidepressants after adjustment for sex, age, cohabitation, socioeconomic position and alcohol consumption (OR 1.43, 95% CI 1.09 to 1.88). The effect was attenuated after further adjustment for baseline depressive symptoms (OR 1.15, 95% CI 0.87 to 1.52). A history of prolonged unemployment predicted use of antidepressants in both models (OR 1.62, 95% CI 1.14 to 2.30 and OR 1.49, 95% CI 1.04 to 2.13, respectively) Compared with participants with neither job insecurity nor unemployment history, the OR for the joint effect of job insecurity and history of prolonged unemployment was substantially higher (OR 1.79, 95% CI 1.15 to 2.79) than the OR for job insecurity (OR 1.02) and unemployment history (OR 1.10) alone in the fully adjusted model. Job insecurity predicts incident use of antidepressants among Danish employees with a history of prolonged unemployment.

  1. SSRI antidepressant use potentiates weight gain in the context of unhealthy lifestyles: results from a 4-year Australian follow-up study.

    PubMed

    Shi, Zumin; Atlantis, Evan; Taylor, Anne W; Gill, Tiffany K; Price, Kay; Appleton, Sarah; Wong, Ma-Li; Licinio, Julio

    2017-08-11

    To examine the association between antidepressant use and weight gain, as well as the interaction with lifestyle factors. Longitudinal study. We used data from 2334 adults from two stages (4.4 years apart) of the North West Adelaide Health Study, including validated diet and lifestyle questionnaires, measured body weight and linked pharmaceutical prescription data. Body weight change. 188 (8.1%) participants had a mean annual number of 1-2 antidepressant prescriptions, and 212 (9.1%) had over two prescriptions. The mean annual weight gain was 0.12, 0.18 and 0.28 kg in non-users, low (1-2 prescriptions/year) and high (>2 prescriptions/year) antidepressant users, respectively. In multivariable regression models, antidepressant use was positively associated with weight gain: high antidepressant users gained an extra 0.22 (95% CI 0.00 to 0.44) kg per year. This association was mainly due to selective serotonin reuptake inhibitor (SSRI) use. High SSRI users gained 0.48 (95% CI 0.20 to 0.76) kg more than non-users. There was no association between tricyclic or other antidepressant use and weight gain. The association between SSRI use and weight gain was stronger among those with high intake of Western diet, greater sedentary activity, and who smoked. SSRIs use was associated with weight gain in the presence of unhealthy behaviours including Western diet, sedentarism and smoking. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  2. Switching and stopping antidepressants

    PubMed Central

    Keks, Nicholas; Hope, Judy; Keogh, Simone

    2016-01-01

    SUMMARY Switching from one antidepressant to another is frequently indicated due to an inadequate treatment response or unacceptable adverse effects. All antidepressant switches must be carried out cautiously and under close observation. Conservative switching strategies involve gradually tapering the first antidepressant followed by an adequate washout period before the new antidepressant is started. This can take a long time and include periods of no treatment with the risk of potentially life-threatening exacerbations of illness. Clinical expertise is needed for more rapid or cross-taper switching as drug toxicity, including serotonin syndrome, may result from inappropriate co-administration of antidepressants. Some antidepressants must not be combined. Antidepressants can cause withdrawal syndromes if discontinued abruptly after prolonged use. Relapse and exacerbation of depression can also occur. Gradual dose reduction over days to weeks reduces the risk and severity of complications. PMID:27346915

  3. Brain Changes in Responders vs. Non-Responders in Chronic Migraine: Markers of Disease Reversal

    PubMed Central

    Hubbard, Catherine S.; Becerra, Lino; Smith, Jonathan H.; DeLange, Justin M.; Smith, Ryan M.; Black, David F.; Welker, Kirk M.; Burstein, Rami; Cutrer, Fred M.; Borsook, David

    2016-01-01

    The aim of this study was to identify structural and functional brain changes that accompanied the transition from chronic (CM; ≥15 headache days/month) to episodic (EM; <15 headache days/month) migraine following prophylactic treatment with onabotulinumtoxinA (BoNT-A). Specifically, we examined whether CM patients responsive to prophylaxis (responders; n = 11), as evidenced by a reversal in disease status (defined by at least a 50% reduction in migraine frequency and <15 headache days/month), compared to CM patients whose migraine frequency remained unchanged (non-responders; n = 12), showed differences in cortical thickness using surface-based morphometry. We also investigated whether areas showing group differences in cortical thickness displayed altered resting-state functional connectivity (RS-FC) using seed-to-voxel analyses. Migraine characteristics measured across groups included disease duration, pain intensity and headache frequency. Patient reports of headache frequency over the 4 weeks prior to (pre-treatment) and following (post-treatment) prophylaxis were compared (post minus pre) and this measure served as the clinical endpoint that determined group assignment. All patients were scanned within 2 weeks of the post-treatment visit. Results revealed that responders showed significant cortical thickening in the right primary somatosensory cortex (SI) and anterior insula (aINS), and left superior temporal gyrus (STG) and pars opercularis (ParsOp) compared to non-responders. In addition, disease duration was negatively correlated with cortical thickness in fronto-parietal and temporo-occipital regions in responders but not non-responders, with the exception of the primary motor cortex (MI) that showed the opposite pattern; disease duration was positively associated with MI cortical thickness in responders versus non-responders. Our seed-based RS-FC analyses revealed anti-correlations between the SI seed and lateral occipital (LOC) and dorsomedial

  4. Anxious Children and Adolescents Non-responding to CBT: Clinical Predictors and Families' Experiences of Therapy.

    PubMed

    Lundkvist-Houndoumadi, Irene; Thastum, Mikael

    2017-01-01

    The purpose of the study was to examine clinical predictors of non-response to manualized cognitive behaviour therapy (CBT) among youths (children and adolescents) with anxiety disorders, and to explore families' perspective on therapy, using a mixed methods approach. Non-response to manualized group CBT was determined among 106 youths of Danish ethnicity (7-17 years old) with a primary anxiety disorder, identified with the Clinical Global Impression of Improvement Scale at the 3-month follow-up. Twenty-four youths (22.6 %) had not responded to treatment, and a logistic regression analysis revealed that youths with a primary diagnosis of social phobia were seven times more likely not to respond, whereas youths with a comorbid mood disorder were almost four times more likely. Families of non-responding youths with primary social phobia and/or a comorbid mood disorder (n = 15) were interviewed, and data were analysed through interpretative phenomenological analysis. Two superordinate themes emerged: youths were not involved in therapy work, and manualized group format posed challenges to families. The mixed methods approach provided new perspectives on the difficulties that may be encountered by families of non-responding youths with a primary social phobia diagnosis and youths with a comorbid mood disorder during manualized group CBT. Clinical implications related to youths' clinical characteristics, and families' experience and suggestions are drawn. Copyright © 2015 John Wiley & Sons, Ltd. Youths with an anxiety disorder, who had a primary social phobia diagnosis and those, who had a comorbid mood disorder, were more likely not to respond to manualized group CBT. Parents of those non-responding youths often considered them as motivated to overcome their difficulties, but due to their symptomatology, they were unreceptive, reluctant and ambivalent and therefore not actively involved in therapy. The non-responding youths with social phobia felt evaluated and

  5. Antidepressant choice in the patient with cardiac disease: lessons from the Cardiac Arrhythmia Suppression Trial (CAST) studies.

    PubMed

    Roose, S P; Glassman, A H

    1994-09-01

    At one point it was believed that the systematic study of the cardiovascular effects of therapeutic levels of tricyclic antidepressants had established the relative safety of these drugs even in patients with significant cardiovascular disease. However, recent studies demonstrating a deleterious effect of antiarrhythmic agents in patients with ischemic heart disease have significant implication for conclusions about tricyclic safety. Studies in cardiology designed to demonstrate that suppression of ventricular arrhythmia in the post-myocardial infarction period would reduce mortality produced the unexpected opposite result, i.e., patients treated with class I antiarrhythmic drugs actually had an increase in their mortality rate. Since tricyclics are classified as type IA antiarrhythmics, it would seem prudent to assume that they have similar risks unless proven otherwise. Other drugs such as the serotonin selective reuptake inhibitors or bupropion, which may be safer than the tricyclics from the cardiovascular perspective, have yet to establish their efficacy in the older and more severely depressed patient population.

  6. Bipolar depression and treatment with antidepressants.

    PubMed

    Goodwin, Guy M

    2012-01-01

    Treatment of bipolar disorder with antidepressants tested almost exclusively in unipolar cases is common but unsupported by an appropriate body of evidence. This anomaly is highlighted by a large Taiwanese study, which implies that patients with depression difficult to treat with antidepressants are quite likely to be diagnosed subsequently with bipolar disorder.

  7. Curcumin as a putative antidepressant.

    PubMed

    Seo, Ho-Jun; Wang, Sheng-Min; Han, Changsu; Lee, Soo-Jung; Patkar, Ashwin A; Masand, Prakash S; Pae, Chi-Un

    2015-03-01

    Due to inadequate efficacy of antidepressants, various new chemical entities and agents of natural origin have been tested for therapeutic efficacy both alone and to augment existing antidepressants, producing varied clinical results. This article summarizes the basic properties of curcumin and its mechanisms of action, with specific emphasis on the etiopathogenesis of depression, preclinical and current clinical evidence, and future research directions, to better understand the possible role of curcumin in treating depression. Curcumin may have antidepressant activities with diverse mechanisms of action involving primarily neurotransmitters, transcription pathways, neurogenesis, the hypothalamic-pituitary-adrenal axis and inflammatory and immune pathways, as demonstrated in various animal and human studies. Current published randomized clinical trials suggest a small, non-significant benefit of curcumin for major depression. More adequately-powered and methodologically improved studies are mandatory.

  8. Development and validation of a flow-injection assay for dissolution studies of the anti-depressant drug venlafaxine.

    PubMed

    Tzanavaras, Paraskevas D; Verdoukas, Aspasia; Themelis, Demetrius G

    2005-12-01

    The first flow-injection method has been developed, optimized and validated for the determination of venlafaxine, an antidepressant drug. The method is based on a direct measurement of the absorbance of the analyte in an acidic medium, at 274 nm. Flow-injection parameters, such as sample injection volume and flow rate, were studied and optimized. The proposed method was validated in terms of linearity, repeatability, detection limit, accuracy and selectivity. Linearity was obeyed in the range 30 - 150 mg L(-1) of venlafaxine, while the detection limit (1.5 mg L(-1)) and repeatability (sr < 1.0%, n = 12) were satisfactory. The sampling rate was 30 h(-1). The results of dissolution studies of venlafaxine tablets obtained by the proposed method were in good agreement with those by high-performance liquid chromatography.

  9. Antidepressant chronotherapeutics for bipolar depression.

    PubMed

    Benedetti, Francesco

    2012-12-01

    Chronotherapeutics refers to treatments based on the principles of circadian rhythm organization and sleep physiology, which control the exposure to environmental stimuli that act on biological rhythms, in order to achieve therapeutic effects in the treatment of psychiatric conditions. It includes manipulations of the sleep-wake cycle such as sleep deprivation and sleep phase advance, and controlled exposure to light and dark. The antidepressant effects of chronotherapeutics are evident in difficult-to-treat conditions such as bipolar depression, which has been associated with extremely low success rates of antidepressant drugs in naturalistic settings and with stable antidepressant response to chronotherapeutics in more than half of the patients. Recent advances in the study of the effects of chronotherapeutics on neurotransmitter systems, and on the biological clock machinery, allow us to pinpoint its mechanism of action and to transform it from a neglected or "orphan" treatment to a powerful clinical instrument in everyday psychiatric practice.

  10. Antidepressant chronotherapeutics for bipolar depression

    PubMed Central

    Benedetti, Francesco

    2012-01-01

    Chronotherapeutics refers to treatments based on the principles of circadian rhythm organization and sleep physiology, which control the exposure to environmental stimuli that act on biological rhythms, in order to achieve therapeutic effects in the treatment of psychiatric conditions. It includes manipulations of the sleep-wake cycle such as sleep deprivation and sleep phase advance, and controlled exposure to light and dark. The antidepressant effects of chronotherapeutics are evident in difficult-to-treat conditions such as bipolar depression, which has been associated with extremely low success rates of antidepressant drugs in naturalistic settings and with stable antidepressant response to chronotherapeutics in more than half of the patients. Recent advances in the study of the effects of chronotherapeutics on neurotransmitter systems, and on the biological clock machinery, allow us to pinpoint its mechanism of action and to transform it from a neglected or “orphan” treatment to a powerful clinical instrument in everyday psychiatric practice. PMID:23393416

  11. Trends in Depression and Antidepressant Prescribing in Children and Adolescents: A Cohort Study in The Health Improvement Network (THIN)

    PubMed Central

    Wijlaars, Linda P. M. M.; Nazareth, Irwin; Petersen, Irene

    2012-01-01

    Background In 2003, the Committee on Safety of Medicines (CSM) advised against treatment with selective serotonin reuptake inhibitors (SSRIs) other than fluoxetine in children, due to a possible increased risk of suicidal behaviour. This study examined the effects of this safety warning on general practitioners' depression diagnosing and prescription behaviour in children. Methods and Findings We identified a cohort of 1,502,753 children (<18 y; registered with GP for >6 m) in The Health Improvement Network (THIN) UK primary care database. Trends in incidence of depression diagnoses, symptoms and antidepressant prescribing were examined 1995–2009, accounting for deprivation, age and gender. We used segmented regression analysis to assess changes in prescription rates. Overall, 45,723 (3%) children had ≥1 depression-related entry in their clinical records. SSRIs were prescribed to 16,925 (1%) of children. SSRI prescription rates decreased from 3.2 (95%CI:3.0,3.3) per 1,000 person-years at risk (PYAR) in 2002 to 1.7 (95%CI:1.7,1.8) per 1,000 PYAR in 2005, but have since risen to 2.7 (95%CI:2.6,2.8) per 1,000 PYAR in 2009. Prescription rates for CSM-contraindicated SSRIs citalopram, sertraline and especially paroxetine dropped dramatically after 2002, while rates for fluoxetine and amitriptyline remained stable. After 2005 rates for all antidepressants, except paroxetine and imipramine, started to rise again. Rates for depression diagnoses dropped from 3.0 (95%CI:2.8,3.1) per 1,000 PYAR in 2002 to 2.0 (95%CI:1.9,2.1) per 1,000 PYAR in 2005 and have been stable since. Recording of symptoms saw a steady increase from 1.0 (95%CI:0.8,1.2) per 1,000 PYAR in 1995 to 4.7 (95%CI:4.5,4.8) per 1,000 PYAR in 2009. Conclusions The rates of depression diagnoses and SSRI prescriptions showed a significant drop around the time of the CSM advice, which was not present in the recording of symptoms. This could indicate caution on the part of GPs in making depression diagnoses and

  12. Novel protective mechanisms of antidepressants against 3-nitropropionic acid induced Huntington's-like symptoms: a comparative study.

    PubMed

    Kumar, Puneet; Kalonia, Harikesh; Kumar, Anil

    2011-10-01

    Huntington's disease (HD) is characterized by progressive degeneration of neurons in the striatum, cortex and other parts of the brain, causing motor and cognitive dysfunction. 3-Nitropropionic acid (3-NP) is a well-known mycotoxin that significantly induces motor dysfunction in animals. Studies suggested the involvement of oxidative stress and nitric oxide mechanisms in HD pathogenesis. Clinical reports have also indicated the neuroprotective potential of antidepressants. Therefore, the present study has been designed to elucidate and compare the mechanistic role of different antidepressants (sertraline, venlafaxine, imipramine and trazodone) and their interaction with nitric oxide modulators if any, against 3-NP-induced neurotoxicity. Systemic 3-NP (10 mg/kg) administration for 14 days significantly reduced locomotor activity, body weight, motor coordination, oxidative defense and impaired mitochondrial complex enzyme activities in the striatum. Sertraline, venlafaxine, imipramine and trazodone treatments significantly improved behavioral, oxidative defense and mitochondrial complex enzyme activities as compared with the 3-NP-treated group. Systemic L-arginine (50 mg/kg) pretreatment with sub-effective dose of sertraline (10 mg/kg), venlafaxine (10 mg/kg), imipramine (10 mg/kg) and trazodone (10 mg/kg) for 14 days significantly attenuated their protective effect. Similarly, L-nitro-arginine methyl ester (L-NAME) (10 mg/kg) pretreatment with sub-effective dose of sertraline (10 mg/kg), venlafaxine (10 mg/kg), imipramine (10 mg/kg) and trazodone (10 mg/kg) for 14 days significantly potentiated their protective effects which were significant as compared with their effect alone, respectively. The results of the present study suggest that a nitric oxide mechanism might be involved in their protective effect against 3-NP-induced neurotoxicity.

  13. Therapeutic Drug Monitoring (TDM) in psychiatry (part I): why studies attempting to correlate drug concentration and antidepressant response don't work.

    PubMed

    Preskorn, Sheldon H

    2014-03-01

    In this column, the first in a series discussing why therapeutic drug monitoring (TDM) is a seriously underutilized tool in psychiatry, the author explains why standard antidepressant registration trials are not able to establish a correlation between antidepressant response and the plasma concentration of biogenic amine antidepressants, such as selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. The problem is that such studies have a poor signal-to- noise ratio. In such studies, approximately one third of participants receiving drug respond specifically because of the drug, one third of participants receiving drug respond not because of the drug but rather because of the "placebo" effect inherent in participating in such a study, and one third of participants on drug do not respond sufficiently to be counted as responders. In analyzing the results of such studies, the data from these last two groups make it impossible to identify whether there is any relationship between drug concentration and antidepressant response. The next column in this series will discuss how TDM can be used as a "personalized medicine" tool to evaluate patients who are at risk for less than optimum response either because they may have much more rapid or much slower clearance of a drug than is usual as well as to identify adherence problems.

  14. Influence of Neuropeptide Y and antidepressants upon cerebral monoamines involved in depression: an in vivo electrochemical study.

    PubMed

    Crespi, Francesco

    2011-08-17

    Neuropeptide Y (NPY) and its receptors are present in the peripheral as well as the central nervous system (CNS). In vitro data have indicated NPY as an important mediator in the regulation of different diseases e.g. related to obesity, anxiety, depression, pain, memory loss and sleep disorders. In particular, studies of NPY levels in the cerebral spinal fluid (CSF) of depressed patients have shown a significant reduction of NPY levels when compared to control subjects. In addition, decreased concentrations of NPY were measured in the brain of suicide victims. These studies suggest that a reduction in cerebral NPY function may be associated with depressive symptoms. In the present work, a putative interaction between NPY, the catecholaminergic and serotonergic systems has been analysed by means of in vivo Differential Pulse Voltammetry (DPV) with treated carbon fibre micro electrodes (mCFE). It appeared that DPV with mCFE is an efficacious tool to monitor in vivo basal levels of catechols (Peak 2) and indoles (Peak 3) in discrete brain regions of rodents. Furthermore, it is shown that the peptidergic signal (Peak 5) simultaneously recorded with Peaks 2 and 3 in the amygdala could correspond to the oxidation of basal endogenous NPY. In addition, pharmacological treatments performed in vivo with exogenous NPY and with Y1 receptor antagonist BIBP3226 have indicated that these compounds interact positively with endogenous catecholaminergic and serotoninergic systems, in a way similar to that of the antidepressants imipramine and fluoxetine. In addition, the observed decrease of endogenous Peak 5 after treatment with imipramine or fluoxetine could be related to the concomitant stimulation of the catecholaminergic system with consequent reduced need for endogenous NPY. This would imply that NPY could be one of the endogenous chemicals acting on the maintenance of the mood. Thus, an antidepressant therapeutic potential of NPY and related compounds (e.g. BIBP3226) could be

  15. Clinical outcomes and genome-wide association for a brain methylation site in an antidepressant pharmacogenetics study in Mexican Americans.

    PubMed

    Wong, Ma-Li; Dong, Chuanhui; Flores, Deborah L; Ehrhart-Bornstein, Monika; Bornstein, Stefan; Arcos-Burgos, Mauricio; Licinio, Julio

    2014-12-01

    The authors compared the effectiveness of fluoxetine and desipramine treatment in a prospective double-blind pharmacogenetics study in first-generation Mexican Americans and examined the role of whole-exome functional gene variations in the patients' antidepressant response. A total of 232 Mexican Americans who met DSM-IV criteria for major depressive disorder were randomly assigned to receive 8 weeks of double-blind treatment with desipramine (50-200 mg/day) or fluoxetine (10-40 mg/day) after a 1-week placebo lead-in period. Outcome measures included the Hamilton Depression Rating Scale (HAM-D), the Hamilton Anxiety Rating Scale, and the Beck Depression Inventory. At week 8, whole-exome genotyping data were obtained for 36 participants who remitted and 29 who did not respond to treatment. Compared with desipramine treatment, fluoxetine treatment was associated with a greater reduction in HAM-D score, higher response and remission rates, shorter time to response and remission, and lower incidences of anticholinergic and cardiovascular side effects. Pharmacogenetics analysis showed that exm-rs1321744 achieved exome-wide significance for treatment remission. This variant is located in a brain methylated DNA immunoprecipitation sequencing site, which suggests that it may be involved in epigenetic regulation of neuronal gene expression. This and two other common gene variants provided a highly accurate cross-validated predictive model for treatment remission of major depression (receiver operating characteristic integral=0.95). Compared with desipramine, fluoxetine treatment showed a more rapid reduction of HAM-D score and a lower incidence of side effects in a population comprising primarily first-generation Mexican Americans with major depression. This study's pharmacogenetics approach strongly implicates the role of functional variants in antidepressant treatment response.

  16. Prevalence of and factors related to the use of antidepressants and benzodiazepines: results from the Singapore Mental Health Study

    PubMed Central

    2013-01-01

    Background Prescription and use of antidepressants and benzodiazepines are common in the general population. Prescription of psychotropic drugs is a complex process: patient, physician and healthcare characteristics mediate, interact and influence it. The current study aimed to establish the prevalence and factors associated with the use of antidepressants (ADs) and benzodiazepines (BZDs) in Singapore. Methods The Singapore Mental Health Study (SMHS) was a nationally representative survey of Singapore Residents aged 18 years and above. Face-to-face interviews were conducted from December 2009 to December 2010. The diagnoses of mental disorders were established using the Composite International Diagnostic Interview version 3.0 (CIDI-3.0). The pharmacoepidemiology section was used to collect information on medication use. Results The overall prevalence estimates for ADs and BZDs use during the 12 months prior to the interview were 1.1% and 1.2% respectively. In all, 2.0% had used ADs and/or BZDs. ‘Help seeking for emotional or mental health problems’ was the most important predictor for the use of ADs and BZDs—help seekers were much more likely to use ADs (adjusted OR: 31.62, 95% CI: 13.36–74.83) and more likely to use BZDs than non-help seekers in the previous 12 months (adjusted OR: 34.38, 95% CI: 12.97–91.16). Only 27.6% of those with 12-month major depressive disorder (MDD) had sought formal medical help for their problems and ADs were being used by just over a quarter of this ‘help-seeking group’ (26.3%). Conclusions We found that the use of ADs and BZDs in our population was relatively low, and ‘help-seeking’ was the most important predictor of the use of ADs and BZDs. In concordance with research from other Western countries, use of ADs was low among those with 12-month MDD. PMID:24053713

  17. [Pharmacogenomics and antidepression research].

    PubMed

    Yamada, Mitsuhiko

    2003-04-01

    Although antidepressants have been used clinically for more than 50 years, no consensus has been reached concerning their precise molecular mechanism of action. Pharmacogenomics is a powerful tool that can be used to identify genes affected by antidepressants or by other effective therapeutic manipulations. Using this tool we have previously identified hundreds of cDNA fragments as antidepressant related genes (ADRGs). Some of these candidate genes may encode common functional molecules induced by chronic antidepressant treatment. Defining the roles of these molecules in drug-induced neural plasticity is likely to transform the course of research on the biological basis of antidepressants. Such detailed knowledge will have profound effects on the diagnosis, prevention, and treatment of depression. Novel biological approaches beyond the "monoamine hypothesis" are expected to evoke paradigm shifts in the future of antidepressant research.

  18. Long-term trend in pediatric antidepressant use, 1983-2007: a population-based study.

    PubMed

    Meng, Xiangfei; D'Arcy, Carl; Tempier, Raymond

    2014-02-01

    Research is needed to clarify and improve our understanding of appropriateness and safety issues concerning antidepressant (AD) treatment. We explored the long-term trend in the dispensing of pediatric ADs using provincial, population-based data from Canada. Data covering 22 ADs were drawn from the Saskatchewan Ministry of Health administrative data files in outpatient settings. The data were for 9 triennial years from 1983 to 2007, a 24-year period, for those aged 0 to 19 in the general population. Descriptive analyses were used. In 1983, 5.9 per 1000 population aged 0 to 19 were dispensed at least 1 AD; this decreased to 5.1 per 1000 population in 1989, and then increased to 15.4 per 1000 population in 2007, with a slower increase after 2004. Both sexes were dispensed more ADs from 1989 onwards, with females being the heavier users. The rate of AD use increased significantly with age, and this trend became more pronounced after 1998. Family physicians were the major prescribers and their prescriptions significantly increased from 1989 to 2004 and decreased in 2007. The use of selective serotonin reuptake inhibitors (SSRIs) was the major reason for the increase. The number of AD scripts per patient also increased. The growth in the prevalence of AD use among children and youth was largely caused by the use of SSRIs. The possibility of safety issues induced by AD use among children and adolescents, and different patterns of medication practice, suggest continuing education is warranted.

  19. Factors Associated With Depressive Symptoms and Use of Antidepressant Medications Among Participants in the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC Studies

    PubMed Central

    Fischer, Michael J.; Xie, Dawei; Jordan, Neil; Kop, Willem J.; Krousel-Wood, Marie; Tamura, Manjula Kurella; Kusek, John W.; Ford, Virginia; Rosen, Leigh K.; Strauss, Louise; Teal, Valerie L.; Yaffe, Kristine; Powe, Neil R.; Lash, James P.

    2012-01-01

    Background Depressive symptoms are correlated with poor health outcomes in adults with chronic kidney disease (CKD). The prevalence, severity, and treatment of depressive symptoms and potential risk factors, including level of kidney function, in diverse populations with CKD have not been well studied. Study Design Cross-sectional analysis Settings and Participants Participants at enrollment into the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC (H-CRIC) Studies. CRIC enrolled Hispanics and non-Hispanics at seven centers from 2003-2007, and H-CRIC enrolled Hispanics at the University of Illinois from 2005-2008. Measurement Depressive symptoms measured by Beck Depression Inventory (BDI) Predictors Demographic and clinical factors Outcomes Elevated depressive symptoms (BDI >= 11) and antidepressant medication use Results Among 3853 participants, 28.5% had evidence of elevated depressive symptoms and 18.2% were using antidepressant medications; 30.8% of persons with elevated depressive symptoms were using antidepressants. The prevalence of elevated depressive symptoms varied by level of kidney function: 25.2% among participants with eGFR ≥ 60 ml/min/1.73m2, and 35.1% of those with eGFR < 30 ml/min/1.73m2. Lower eGFR (OR per 10 ml/min/1.73m2 decrease, 1.09; 95% CI, 1.03-1.16), Hispanic ethnicity (OR, 1.65; 95% CI, 1.12-2.45), and non-Hispanic black race (OR, 1.43; 95% CI, 1.17-1.74) were each associated with increased odds of elevated depressive symptoms after controlling for other factors. In regression analyses incorporating BDI score, while female sex was associated with a greater odds of antidepressant use, Hispanic ethnicity, non-Hispanic black race, and higher levels of urine albumin were associated with decreased odds of antidepressant use (p<0.05 for each). Limitations Absence of clinical diagnosis of depression and use of non-pharmacologic treatments Conclusions Although elevated depressive symptoms were common in individuals with CKD, use of

  20. 'In my life antidepressants have been…': a qualitative analysis of users' diverse experiences with antidepressants.

    PubMed

    Gibson, Kerry; Cartwright, Claire; Read, John

    2016-05-11

    While mental health professionals have focused on concerns about whether antidepressants work on a neurochemical level it is important to understand the meaning this medication holds in the lives of people who use it. This study explores diversity in the experience of antidepressant users. One thousand seven hundred forty-seven New Zealand antidepressant users responded to an open-ended question about their experience of antidepressants. This was analysed using content and thematic analysis. There was considerable diversity in participants' responses including positive (54 %), negative (16 %) and mixed (28 %) experiences with antidepressants. Those with positive experiences saw antidepressants as a necessary treatment for a 'disease', a life saver, a way of meeting social obligations, dealing with difficult circumstances or a stepping stone to further help. Negative themes described antidepressants as being ineffective, having unbearable side effects, undermining emotional authenticity, masking real problems and reducing the experience of control. Mixed experience themes showed how participants weighed up the unpleasant side effects against the benefits, felt calmer but less like themselves, struggled to find the one or dosage and felt stuck with continuing on antidepressants when they wished to stop. Mental health professions need to recognize that antidepressants are not a 'one size fits all' solution.

  1. Enhancement of antidepressant-like activity by joint administration of imipramine and magnesium in the forced swim test: Behavioral and pharmacokinetic studies in mice.

    PubMed

    Poleszak, Ewa; Wlaź, Piotr; Szewczyk, Bernadeta; Kedzierska, Ewa; Wyska, Elzbieta; Librowski, Tadeusz; Szymura-Oleksiak, Joanna; Fidecka, Sylwia; Pilc, Andrzej; Nowak, Gabriel

    2005-07-01

    The effect of joint administration of imipramine (IMI) and magnesium (Mg) on antidepressant-like activity was studied in mice using forced swim test (FST). Mg doses ineffective per se (5 and 10 mg/kg) given jointly with IMI also at ineffective doses (10 and 15 mg/kg) resulted in a potent reduction in the immobility time. Since these combined treatments did not influence locomotor activity, the antidepressant-like activity was not due to non-specific behavioral activation. Moreover, we estimated the effect of joint administration of magnesium and IMI in FST on serum and brain magnesium, IMI and its active metabolite desipramine (DMI) concentrations in mice. Swim stress (mice subjected to FST) increased the magnesium concentration in serum and decreased it in the brain compared to naive animals. Moreover administration of IMI increased (normalized) magnesium brain concentration, without influence on the serum level. Joint administration of IMI and magnesium did not influence magnesium (compared with FST) or IMI and DMI (compared with IMI treatment alone) concentrations in both examined tissues. The present data demonstrated an enhancement of the antidepressant-like effect by joint administration of IMI and magnesium in the FST, and further indicate the particular role of magnesium in the antidepressant action. Since there was no increase in IMI, DMI or magnesium concentration after joint administration of magnesium and IMI, the data suggest that pharmacodynamic rather than pharmacokinetic interaction between magnesium and IMI is accountable for behavioral effect in the FST.

  2. Factors associated with depressive symptoms and use of antidepressant medications among participants in the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC Studies.

    PubMed

    Fischer, Michael J; Xie, Dawei; Jordan, Neil; Kop, Willem J; Krousel-Wood, Marie; Kurella Tamura, Manjula; Kusek, John W; Ford, Virginia; Rosen, Leigh K; Strauss, Louise; Teal, Valerie L; Yaffe, Kristine; Powe, Neil R; Lash, James P

    2012-07-01

    Depressive symptoms are correlated with poor health outcomes in adults with chronic kidney disease (CKD). The prevalence, severity, and treatment of depressive symptoms and potential risk factors, including level of kidney function, in diverse populations with CKD have not been well studied. Cross-sectional analysis. Participants at enrollment into the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC (H-CRIC) Studies. CRIC enrolled Hispanics and non-Hispanics at 7 centers in 2003-2007, and H-CRIC enrolled Hispanics at the University of Illinois in 2005-2008. Depressive symptoms measured by Beck Depression Inventory (BDI). Demographic and clinical factors. Elevated depressive symptoms (BDI score ≥11) and antidepressant medication use. Of 3,853 participants, 27.4% had evidence of elevated depressive symptoms and 18.2% were using antidepressant medications; 31.0% of persons with elevated depressive symptoms were using antidepressants. The prevalence of elevated depressive symptoms varied by level of kidney function: 23.6% for participants with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m(2) and 33.8% of those with eGFR <30 mL/min/1.73 m(2). Lower eGFR (OR per 10-mL/min/1.73 m(2) decrease, 1.10; 95% CI, 1.04-1.17), and non-Hispanic black race (OR, 1.42; 95% CI, 1.16-1.74) were each associated with increased odds of elevated depressive symptoms after controlling for other factors. In regression analyses incorporating BDI score, whereas female sex was associated with greater odds of antidepressant use, Hispanic ethnicity, non-Hispanic black race, and higher urine albumin levels were associated with decreased odds of antidepressant use (P < 0.05 for each). Absence of clinical diagnosis of depression and use of nonpharmacologic treatments. Although elevated depressive symptoms were common in individuals with CKD, use of antidepressant medications is low. Individuals of racial and ethnic minority background and with more advanced CKD had a

  3. Prevalence and Prescription of Antidepressants in Depression with Somatic Comorbidity in Asia: The Research on East Asian Psychotropic Prescription Patterns Study

    PubMed Central

    Chen, Chao; Si, Tian-Mei; Xiang, Yu-Tao; Ungvari, Gabor S; Wang, Chuan-Yue; He, Yan-Ling; Kua, Ee-Heok; Fujii, Senta; Sim, Kang; Trivedi, Jitendra K; Chung, Eun-Kee; Udomratn, Pichet; Chee, Kok-Yoon; Sartorius, Norman; Tan, Chay-Hoon; Shinfuku, Naotaka

    2015-01-01

    Background: Depression is often comorbid with chronic somatic diseases. Few previous studies have investigated the prevalence of somatic diseases in depression or the prescription pattern of antidepressants in comorbidly depressed patients in Asia. This study aimed to investigate the prevalence of somatic comorbidity (SC) in depression and compared the prescriptions of antidepressants in depressed patients with and without SC. Methods: A total of 2320 patients treated with antidepressants in 8 Asian countries were examined, and a diagnosis was based on the International Classification of Disease, 10th revision. We listed 17 common chronic somatic diseases. Patients’ socio-demographic and clinical characteristics and psychotropic drug prescriptions were recorded using a standardized protocol and data collection procedure. Results: Of the patients examined, 1240 were diagnosed with depression and 30% of them (n = 375) had SC. The most common comorbid condition was diabetes (23.7%). The patients with SC were more likely to seek help at a general hospital (74.7% vs. 47.2%), and had a higher incidence of symptoms involving sadness, disturbed sleep, and poor appetite. Noradrenergic and specific serotonergic antidepressant was prescribed more for patients with SC than for those without SC (30.4% vs. 22.9%). Conclusions: SC is common in depressed Asian patients. It is important to strengthen the recognition of depression, especially in general hospitals and when patients report some somatic discomfort. It is also a matter of urgency to establish evidence-based guidelines for the use of new antidepressants in depressed patients with SC. PMID:25836602

  4. Neuroplasticity and second messenger pathways in antidepressant efficacy: pharmacogenetic results from a prospective trial investigating treatment resistance.

    PubMed

    Fabbri, Chiara; Crisafulli, Concetta; Calati, Raffaella; Albani, Diego; Forloni, Gianluigi; Calabrò, Marco; Martines, Rosalba; Kasper, Siegfried; Zohar, Joseph; Juven-Wetzler, Alzbeta; Souery, Daniel; Montgomery, Stuart; Mendlewicz, Julien; Serretti, Alessandro

    2017-03-04

    Genes belonging to neuroplasticity, monoamine, circadian rhythm, and transcription factor pathways were investigated as modulators of antidepressant efficacy. The present study aimed (1) to replicate previous findings in an independent sample with treatment-resistant depression (TRD), and (2) to perform a pathway analysis to investigate the possible molecular mechanisms involved. 220 patients with major depressive disorder who were non-responders to a previous antidepressant were treated with venlafaxine for 4-6 weeks and in case of non-response with escitalopram for 4-6 weeks. Symptoms were assessed using the Montgomery Asberg Depression Rating Scale. The phenotypes were response and remission to venlafaxine, non-response (TRDA) and non-remission (TRDB) to neither venlafaxine nor escitalopram. 50 tag SNPs in 14 genes belonging to the pathways of interest were tested for association with phenotypes. Molecular pathways (KEGG database) that included one or more of the genes associated with the phenotypes were investigated also in the STAR*D sample. The associations between ZNF804A rs7603001 and response, CREB1 rs2254137 and remission were replicated, as well as CHL1 rs2133402 and lower risk of TRD. Other CHL1 SNPs were potential predictors of TRD (rs1516340, rs2272522, rs1516338, rs2133402). The MAPK1 rs6928 SNP was consistently associated with all the phenotypes. The protein processing in endoplasmic reticulum pathway (hsa04141) was the best pathway that may explain the mechanisms of MAPK1 involvement in antidepressant response. Signals in genes previously associated with antidepressant efficacy were confirmed for CREB1, ZNF804A and CHL1. These genes play pivotal roles in synaptic plasticity, neural activity and connectivity.

  5. Nanoparticle mediated brain targeted delivery of gallic acid: in vivo behavioral and biochemical studies for improved antioxidant and antidepressant-like activity.

    PubMed

    Nagpal, Kalpana; Singh, Shailendra Kumar; Mishra, Dina Nath

    2012-11-01

    Gallic acid had been reported to possess antidepressant like activity, which may be attributed to its CNS effects like increase in reduced glutathione levels, increased catalase activity and decreased malonaldehyde levels in brain. This study was designed to enhance the antidepressant-like activity of gallic acid (GA) using nanoparticulate delivery system in swiss male albino mice and to explore the possible underlying mechanisms for this activity. GA loaded chitosan nanoparticles (GANP) and corresponding tween 80 coated batch (cGANP) were formulated for brain targeting of GA and characterized for physicochemical parameters, morphology, differential scanning calorimetry and in vitro drug release. GA, GANP, cGANP (dose equivalent to GA 10 mg/kg, i.p.) and positive control drug, Fluoxetine (10 mg/kg, i.p.) were administered for successive seven days to male swiss albino mice. Then, the in vivo antidepressant-like activity was evaluated using Despair Swim Test (DST) and Tail Suspension Test (TST); along with the evaluation of MAO-A activity, reduced glutathione, malonaldehyde level, catalase and locomotor activity in mice. KEYFINDINGS: cGANP (equivalent to 10 mg/kg, i.p.) significantly decreased immobility period of mice in DST and TST, indicating significant antidepressant-like activity. There was no significant effect on locomotor activity of the mice by GA and its nanoparticle formulations. cGANP (10 mg/kg, i.p.) significantly decreased Monoamine oxidase-A (MAO-A) activity, malondialdehyde levels, and catalase activity in mice. GA possess significant antidepressant like activity and ligand coated nanoparticle approach with improved brain targeting may serve as an effective approach to enhance such effect.

  6. Impact of Pretreatment With Antidepressants on the Efficacy of Duloxetine in Terms of Mood Symptoms and Functioning: An Analysis of 15 Pooled Major Depressive Disorder Studies

    PubMed Central

    Barros, Bruno R.; Schacht, Alexander; Happich, Michael; Televantou, Foula; Berggren, Lovisa; Walker, Daniel J.

    2014-01-01

    Objective: This post hoc analysis aimed to determine whether patients with major depressive disorder (MDD) in duloxetine trials who were antidepressant naive or who were previously exposed to antidepressants exhibited differences in efficacy and functioning. Method: Data were pooled from 15 double-blind, placebo- and/or active-controlled duloxetine trials of adult patients with MDD conducted by Eli Lilly and Company. The individual studies took place between March 2000 and November 2009. Data were analyzed using 4 pretreatment subgroups: first-episode never treated, multiple-episode never treated, treated previously only with selective serotonin reuptake inhibitors (SSRIs), and previously treated with antidepressants other than just SSRIs. Measures included the 17-item Hamilton Depression Rating Scale (HDRS-17) total and somatic symptom subscale scores, Montgomery-Asberg Depression Rating Scale (MADRS) total score, and Sheehan Disability Scale total score. Response rates (50% and 30%) were based on the HDRS-17 total score and remission rates on either the HDRS-17 or MADRS total score. Results: Response and remission rates were significantly greater (P < .05 in 11 of 12 comparisons) for duloxetine versus placebo in the 4 subgroups. A trend of greater response and remission occurred for first-episode versus multiple-episode patients; both groups were generally higher than the antidepressant-treated groups. Mean changes in efficacy measures were mostly significantly greater (P < .05 in 13 of 16 comparisons) for duloxetine versus placebo within each pretreatment subgroup, with some (P < .05 in 2 of 24 comparisons) significant interaction effects between subgroups on HDRS-17 total and somatic symptoms scores. Conclusions: Duloxetine was generally superior to placebo on response and remission rates and in mean change on efficacy measures. Response and remission rates were numerically greater for first-episode versus multiple-episode and drug-treated patients. Mean change

  7. Genetic variability at HPA axis in major depression and clinical response to antidepressant treatment.

    PubMed

    Papiol, Sergi; Arias, Bárbara; Gastó, Cristóbal; Gutiérrez, Blanca; Catalán, Rosa; Fañanás, Lourdes

    2007-12-01

    Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been observed in major depression. Normalization of HPA axis has been suggested to play a role in the mechanisms of action of antidepressants. Our aim was to investigate the influence of genetic variants in CRHR1, CRHR2, CRH-BP and FKBP5 genes on both the vulnerability for depression and the response to antidepressant treatment. The sample consisted of 159 depressive outpatients and 96 healthy controls of Spanish origin. Patients were assessed for clinical features including, among others, age of onset, seasonality or suicidal behavior. The episode was treated with citalopram and followed along 12 weeks. Severity of symptoms was evaluated at the inclusion and then monthly along the follow-up using a 21-item Hamilton Depression Rating Score (HDRS). SNPs were assayed using Applied Biosystems SNaP-Shot and TaqMan technology. rs110402, in CRHR1 gene, was associated with an increased risk to present a seasonal pattern and an early age of onset of the first depressive episode. Allele G carriers of rs2270007 of CRHR2 gene, showed a worse overall response to citalopram along time of follow-up (Genotype effect F=7.45, P=0.007). G allele carriers showed 2.93 increased risk (95% CI [1.24-6.90]) for non-responding at 4th week to citalopram treatment (chi(2)=7.59, df=1, P=0.006). On the light of the moderate sample size, associations based on the mentioned polymorphisms need to be considered with caution and require further replication studies in other samples. Variability at genes encoding proteins with a pivotal role in HPA axis regulation seems to influence i) the expression of severity variables of the depressive spectrum including early age of onset or a seasonal pattern and ii) the interindividual variation in clinical response to SSRI antidepressants.

  8. Antidepressants for patients with tinnitus.

    PubMed

    Baldo, Paolo; Doree, Carolyn; Molin, Paola; McFerran, Don; Cecco, Sara

    2012-09-12

    This is an update of a Cochrane review first published in The Cochrane Library in Issue 4, 2006 and previously updated in 2009.Tinnitus is described as the perception of sound or noise in the absence of real acoustic stimulation. It has been compared with chronic pain, and may be associated with depression or depressive symptoms which can affect quality of life and the ability to work. Antidepressant drugs have been used to treat tinnitus in patients with and without depressive symptoms. To assess the effectiveness of antidepressants in the treatment of tinnitus and to ascertain whether any benefit is due to a direct tinnitus effect or a secondary effect due to treatment of concomitant depressive states. We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; PsycINFO; CINAHL; Web of Science; BIOSIS; ICTRP and additional sources for published and unpublished trials. The date of the most recent search was 5 January 2012. Randomised controlled clinical studies of antidepressant drugs versus placebo in patients with tinnitus. Two authors critically appraised the retrieved studies and extracted data independently. Where necessary we contacted study authors for further information. Six trials involving 610 patients were included. Trial quality was generally low. Four of the trials looked at the effect of tricyclic antidepressants on tinnitus, investigating 405 patients. One trial investigated the effect of a selective serotonin reuptake inhibitor (SSRI) in a group of 120 patients. One study investigated trazodone, an atypical antidepressant, versus placebo. Only the trial using the SSRI drug reached the highest quality standard. None of the other included trials met the highest quality standard, due to use of inadequate outcome measures, large drop-out rates or failure to separate the effects on tinnitus from the effects on symptoms of anxiety and depression. All the

  9. Antidepressants for patients with tinnitus.

    PubMed

    Baldo, P; Doree, C; Lazzarini, R; Molin, P; McFerran, D J

    2006-10-18

    Tinnitus is described as the perception of sound or noise in the absence of real acoustic stimulation. It has been compared with chronic pain, and may be associated with depression or depressive symptoms which can affect quality of life and the ability to work. Antidepressant drugs have been used to treat tinnitus in patients with and without depressive symptoms. To assess the effectiveness of antidepressants in the treatment of tinnitus and to ascertain whether any benefit was due to a direct tinnitus effect or a secondary effect due to treatment of concomitant depressive states. We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) The Cochrane Library Issue 1, 2006); MEDLINE (January 1951 to 2006); EMBASE (1974 to 2006), CINAHL (to 2006), PSYCINFO (to 2006), LILACS (to 2006), and Cambridge Scientific Abstracts. The date of the most recent search was March 2006. Randomised controlled clinical studies of antidepressant drugs versus placebo in patients with tinnitus. The studies retrieved were critically appraised and data extracted independently by two authors. Where necessary study authors were contacted for further information. Five trials involving 525 patients were included. Four of these trials looked at the effect of tricyclic antidepressants on tinnitus, investigating 405 patients. One trial investigated the effect of a selective serotonin reuptake inhibitor (SSRI) in a group of 120 patients. No trials involving other antidepressant agents met the inclusion criteria. Only the trial using the SSRI drug met the highest quality standard. None of the other included trials met the highest quality standard, due to use of inadequate outcome measures, large drop out rates or failure to separate the effects on tinnitus from the effects on symptoms of anxiety and depression. All the trials assessing tricyclic antidepressants suggested that there was a slight improvement in tinnitus

  10. Safety and tolerability of dexmecamylamine (TC-5214) adjunct to ongoing antidepressant therapy in patients with major depressive disorder and an inadequate response to antidepressant therapy: results of a long-term study.

    PubMed

    Tummala, Raj; Desai, Dhaval; Szamosi, Johan; Wilson, Ellis; Hosford, David; Dunbar, Geoffrey; Eriksson, Hans

    2015-02-01

    Safety and tolerability are important considerations when selecting patients' treatment for major depressive disorder. We report the long-term safety and tolerability of the nicotinic channel modulator dexmecamylamine (TC-5214), adjunct to selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs) in patients with major depressive disorder and who had an inadequate response to antidepressants. This 52-week, double-blind, placebo-controlled study explored the long-term safety and tolerability of dexmecamylamine. Patients were randomized 3:1 to receive flexibly dosed dexmecamylamine 1 to 4 mg adjunct to SSRI/SNRI or placebo plus SSRI/SNRI. The patient population comprised inadequate responders from 2 Phase III acute dexmecamylamine studies (NCT01157078 [study 002], NCT01153347 [study 004]) and de novo patients who responded inadequately during a 6-week open-label antidepressant treatment period preceding randomization. Safety and tolerability were assessed by monitoring adverse events, vital signs, and physical and laboratory parameters. Descriptive statistical analyses were performed on most efficacy-related end points. Sustained efficacy was analyzed using logistic regression. Overall, 813 patients were randomized (610 received dexmecamylamine, 203 received placebo). In total, 82.4% and 84.6% of patients, respectively, experienced an adverse event. Adverse events occurring more frequently with dexmecamylamine vs placebo were constipation (19.6% vs 6.0%), dizziness (12.0% vs 7.0%), and dry mouth (9.7% vs 5.0%). Back pain (2.8% vs 8.5%), weight increase (4.4% vs 7.0%), and fatigue (5.6 % vs 7.5%) occurred more frequently in placebo-treated patients. No notable differences were observed between dexmecamylamine and placebo for any secondary end point. In this long-term study, safety and tolerability of dexmecamylamine were consistent with that reported in acute Phase III studies of dexmecamylamine.

  11. Pharmacogenetics of antidepressant response

    PubMed Central

    Porcelli, Stefano; Drago, Antonio; Fabbri, Chiara; Gibiino, Sara; Calati, Raffaella; Serretti, Alessandro

    2011-01-01

    Personalized medicine — the adaptation of therapies based on an individual’s genetic and molecular profile — is one of the most promising aspects of modern medicine. The identification of the relation between genotype and drug response, including both the therapeutic effect and side effect profile, is expected to deeply affect medical practice. In this paper, we review the current knowledge about the genes related to antidepressant treatment response and provide methodologic proposals for future studies. We have mainly focused on genes associated with pharmacodynamics, for which a list of promising genes has been identified despite some inconsistency across studies. We have also synthesized the main results for pharmacokinetic genes, although so far they seem less relevant than those for pharmacodynamic genes. We discuss possible reasons for these inconsistent findings and propose new study designs. PMID:21172166

  12. Propensity Score Matching in Nonrandomized Studies: A Concept Simply Explained Using Antidepressant Treatment During Pregnancy as an Example.

    PubMed

    Andrade, Chittaranjan

    2017-02-01

    In prospective and retrospective observational studies, such as those that examine the effects of antidepressant drugs for the treatment of depression during pregnancy, patients are not randomized to whatever treatments they do or do not receive. As a result, treatment groups may be unbalanced for a wide range of sociodemographic and clinical variables. In such studies, because the illness (and its correlates) for which the treatment is indicated may itself influence the study outcomes, the use of the treatment becomes indirectly linked to these outcomes (this is known as confounding by indication), and the effects of treatment and illness on the study outcomes are difficult if not impossible to separate. Case-control research designs, regression analyses that adjust for independent variables, and propensity score matching are ways in which baseline differences between groups and confounding by indication are statistically addressed. This article examines the concepts involved, explains what is done in propensity score matching procedures, and discusses the advantages and limitations of propensity score matching. Whereas propensity score matching can substantially reduce baseline differences between groups in observational studies, it can never correct for unmeasured confounds; therefore, cause-effect relationships can never be deduced from such studies. However, in situations in which gold standard randomized controlled trials are impractical, researchers must make do with statistical approaches such as propensity score matching.

  13. Circulating Plasma Micro RNAs in Patients with Major Depressive Disorder Treated with Antidepressants: A Pilot Study

    PubMed Central

    Enatescu, Virgil Radu; Papava, Ion; Enatescu, Ileana; Antonescu, Mirela; Anghel, Andrei; Seclaman, Edward

    2016-01-01

    Objective Significant progress was made in the understanding etiopathogenic factors related to MDD, including through research on the role of micro RNAs (miRs). We investigated plasma miRs as potential markers for MDD in patients treated with antidepressants. Methods At the initiation and at the end of twelve weeks of treatment, blood samples were collected and a structured diagnostic interview and a standardized depression rating scale for the presence and severity of major depression were done. The average decrease in HAMD score was 76.89%. Plasma miR expression profiling was performed by real time PCR. The lists of up-regulated (cut-off=2) and down-regulated miRs were imported into the miRWalk2.0 algorithm and used for target predictions. KEGG database pathways analysis was used to retrieve the pathways significantly targeted by at least two of the miRs. Results Of the 222 miRs detected in plasma samples of MDD patients, 40 were differentially expressed after treatment. Twenty-three miRs were significantly overexpressed with fold changes between 1.85 and 25.42, and 17 miRs were significantly downregulated with fold changes from 0.28 to 0.68. Pathway analysis revealed a list of 29 pathways for up-regulated miRs, and 20 pathways for down-regulated miRs. Six dysregulated miRs are common to all the top five pathways (Wnt signaling, Cancer, Endocytosis, Axon guidance, MAPK signaling): miR-146a-5p, miR-146b-5p, miR-221-3p, miR-24-3p, miR-26a-5p. Conclusion Overall, our miRWalk analysis of changes in plasma microRNAs after treatment of patients with major depression might open a new avenue for the understanding of Escitalopram mode of action and for its side effects. PMID:27757134

  14. Antidepressants and platinum drugs.

    PubMed

    Engelmann, Brigitte J; Ryan, John J; Farrell, Nicholas P

    2014-01-01

    Antidepressants are frequently prescribed concurrently with anti-cancer drugs and may have synergistic, additive or antagonistic effects. The present work investigated the effect of antidepressants on the cytotoxicity of platinum agents cisplatin, carboplatin and oxaliplatin. The cytotoxicity of platinum drugs alone or in combination with antidepressants was measured in HCT116 wild-type (wt), HCT116 (p53 -/-), HT-29, SKOV3 and A2780 cells using an apoptosis-based assay. The effect of antidepressants on platinum cytotoxicity is both cell type- and drug dependent. Mostly additive effects were observed. Desipramine and fluoxetine caused the greatest effects, with cisplatin in general being most sensitive to their presence. There is little effect of p53 status on the drug-drug interaction while the calmodulin inhibitor W7 augmented cisplatin cytotoxicity relative to carboplatin and oxaliplatin. The drug-drug interaction between antidepressants and platinum anti-cancer agents requires detailed evaluation for optimization of patient care.

  15. [Antidepressants in epilepsy].

    PubMed

    Castaño-Monsalve, Beatriz

    2013-08-01

    Depression is a common condition in patients with epilepsy that entails a deterioration of the quality of life of this population and that, therefore, requires appropriate treatment. The potential risk of antidepressants in relation to the seizure threshold is overestimated by many professionals, and this has an influence when it comes to making the decision to treat them. It sometimes means that the patients do not receive antidepressant drugs. In this regard, the aim of this review is to present the current state of the art in terms of the safety of antidepressants in patients with epilepsy. A search of the medical literature was conducted and, following its analysis, the most significant results are presented. Current information indicates that most antidepressants are safe for epileptic patients at therapeutic doses and that the risk of seizures occurs mainly in cases of overdose. Preferred drugs for treating depression in epilepsy are serotonin reuptake inhibitors. Bupropion and tricyclic antidepressants must be avoided.

  16. [Continued use of hypnotic initiated as part of antidepressant treatment].

    PubMed

    Danel, Antoine; Amariei, Alina; Sayoud, Ashmahane; Danel, Thierry; Plancke, Laurent

    2015-01-01

    Chronic hypnotic prescription is common, but not recommended. This study analysed whether hypnotic use at the beginning of antidepressant treatment could be the starting point for future hypnotic use. Concomitant hypnotic and antidepressant prescriptions were retrieved from the National Health Insurance Fund for employees of the Nord-Pas-de-Calais database. Dispensing of hypnotics during the two quarters following discontinuation of antidepressant treatment was investigated. 8.9% of patients continued using hypnotics after having stopped antidepressants. Factors associated with this continued dispensing were female gender, age greater than or equal to 45 years, quarterly dispensing of hypnotics during antidepressant treatment, dispensing of three or more hypnotics per quarter during antidepressant treatment, and previous dispensing of opioid substitution therapy. A minority of patients continued using hypnotics after stopping antidepressant treatment initiated with hypnotics.

  17. Pharmacist self-reported antidepressant medication counseling.

    PubMed

    Cannon-Breland, Michelle L; Westrick, Salisa C; Kavookjian, Jan; Berger, Bruce A; Shannon, David M; Lorenz, Raymond A

    2013-01-01

    To identify the extent of pharmacists' self-reported antidepressant counseling (SRAC) and to identify factors that may affect pharmacists' decisions to provide antidepressant counseling. Cross-sectional study. Alabama community pharmacies in 2011. Full-time pharmacists from 600 community pharmacies. Self-administered survey; three mail contacts with alternate electronic surveys were used. Pharmacists' SRAC behavior and its relationship with pharmacists' illness perceptions of depression, self-efficacy, and organizational and environmental influences. 600 surveys were sent; 22 were undeliverable, 1 was partially completed (<80% questions answered), and 118 were completed (20.6% overall response rate). Pharmacists reported low rates of involvement in antidepressant counseling; 61% reported assessing patient knowledge and understanding of depression, and 36% discussed options for managing adverse effects with no more than a few patients. More than one-quarter (28.6%) never asked patients whether they had barriers to taking antidepressants. Pharmacists' perceptions regarding consequences, control/cure, and the episodic nature of depression, as well as their self-efficacy, had significant relationships ( P < 0.05) with pharmacists' involvement in antidepressant counseling. Low rates of pharmacists' involvement in antidepressant counseling were reported. Pharmacists must become more involved in counseling patients about their antidepressant medications and overcoming barriers preventing greater involvement.

  18. Oxidation of tricyclic antidepressant drugs with chloramine-T in acidic solutions: kinetic, mechanistic and thermodynamic studies.

    PubMed

    Sukhdev, Anu; Puttaswamy, Puttaswamy

    2013-12-01

    The kinetics of the oxidation of two tricyclic antidepressants (TCA) namely, imipramine (IMP) and clomipramine (CLM) with sodium N-chloro-p-toluenesulfonamide or chloramine-T (CAT) in HClO4 medium was studied at 300 K. The two reactions followed identical kinetics with a first-order dependence of rate on [CAT]o and fractional order dependence on [TCA]o. The reaction is catalyzed by H(+) ions with a fractional order dependence. The reaction was studied at different temperatures and activation parameters were evaluated. The reaction constants involved in the mechanism were computed. The solvent isotope effect was studied using D2O. Addition of p-toluenesulfonamide retards the reaction rate. The rate increased with decreasing dielectric constant of the medium. Variation of ionic strength of the medium and addition of halide ions (Cl(-) or Br(-)) showed no effect on the rate. The stoichiometry of the reaction was found to be 1:1 and the oxidation products were identified as imipramine-5-N-oxide and clomipramine-5-N-oxide. The rate of oxidation of IMP is faster than CLM. The observed results have been explained in terms of a mechanism and a relevant rate law has been deduced.

  19. Changes in dream experience in relation with antidepressant escitalopram treatment in depressed female patients: a preliminary study.

    PubMed

    Quartini, Adele; Anastasia, Annalisa; Bersani, Francesco Saverio; Melcore, Claudia; Albano, Gabriella; Colletti, Chiara; Valeriani, Giuseppe; Bersani, Giuseppe

    2014-01-01

    Sleep disturbances have long been considered as a cardinal symptom of endogenous depression and dreams in depressed patients usually differ from those of healthy people. The aim of the present study was to investigate dream subjective experiences and their modifications in relation to clinical response in a group of escitalopram-treated depressed patients. Twenty-seven female patients meeting DSM-IV-TR criteria for Major Depressive Disorder (MDD) and starting SSRI therapy were included in the study. Data about psychopathological status and dreaming subjective experiences were collected at baseline (T0), 4 weeks after the beginning of the treatment (T1) and after further 4 weeks of therapy (T2). At T0 dream experience was impaired and negatively toned. Concomitantly with the decrease of symptoms severity, the 8-week escitalopram treatment yielded to significant improvements in the recall of both quantity and quality of dreams; those patients whit lower clinical benefits kept on reporting impaired dream experiences. The results of the present study evidence how the changes in some specific dreaming characteristics, such as the subjective recall of dream activity, the dream recall quality, the dream emotional content and the dream complexity represent reliable markers of the effectiveness of antidepressant therapy.

  20. Docking studies of antidepressants against single crystal structure of tryptophan 2, 3-dioxygenase using Molegro Virtual Docker software.

    PubMed

    Dawood, Shazia; Zarina, Shamshad; Bano, Samina

    2014-09-01

    Tryptophan 2, 3-dioxygenase (TDO) a heme containing enzyme found in mammalian liver is responsible for tryptophan (Trp) catabolism. Trp is an essential amino acid that is degraded in to N-formylkynurenine by the action of TDO. The protein ligand interaction plays a significant role in structural based drug designing. The current study illustrates the binding of established antidepressants (ADs) against TDO enzyme using in-silico docking studies. For this purpose, Fluoxetine, Paroxetine, Sertraline, Fluvoxamine, Seproxetine, Citalopram, Moclobamide, Hyperforin and Amoxepine were selected. In-silico docking studies were carried out using Molegro Virtual Docker (MVD) software. Docking results show that all ADs fit well in the active site of TDO moreover Hyperforin and Paroxetine exhibited high docking scores of -152.484k cal/mol and -139.706k cal/mol, respectively. It is concluded that Hyperforin and Paroxetine are possible lead molecules because of their high docking scores as compared to other ADs examined. Therefore, these two ADs stand as potent inhibitors of TDO enzyme.

  1. Influence of antidepressants on hemostasis

    PubMed Central

    Halperin, Demian; Reber, Guido

    2007-01-01

    Antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), are widely used for the treatment of depression and anxious disorders. The observation that depression is an independent risk factor for cardiovascular mortality and morbidity in patients with ischemic heart disease, the assessment of the central role of serotonin in pathophysiological mechanisms of depression, and reports of cases of abnormal bleeding associated with antidepressant therapy have led to investigations of the influence of antidepressants on hemostasis markers. In this review, we summarize data regarding modifications of these markers, drawn from clinical studies and case reports. We observed an association between the type of antidepressant drug and the number of abnormal bleeding case reports, with or without modifications of hemostasis markers. Drugs with the highest degree of serotonin reuptake inhibition - fluoxetine, paroxetine, and sertraline - are more frequently associated with abnormal bleeding and modifications of hemostasis markers. The most frequent hemostatic abnormalities are decreased platelet aggregability and activity, and prolongation of bleeding time. Patients with a history of coagulation disorders, especially suspected or documented thrombocytopenia or platelet disorder, should be monitored in case of prescription of any serotonin reuptake inhibitor (SRI). Platelet dysfunction, coagulation disorder, and von Willebrand disease should be sought in any case of abnormal bleeding occurring during treatment with an SRI. Also, a non-SSRI antidepressant should be favored over an SSRI or an SRI in such a context. Considering the difficulty in performing platelet aggregation tests, which are the most sensitive in SRI-associated bleeding, and the low sensitivity of hemostasis tests when performed in case of uncomplicated bleeding in the general population, establishing guidelines for the assessment of SRI-associated bleeding complications remains a challenge

  2. BDNF — a key transducer of antidepressant effects

    PubMed Central

    Björkholm, Carl; Monteggia, Lisa M.

    2016-01-01

    How do antidepressants elicit an antidepressant response? Here, we review accumulating evidence that the neurotrophin brain-derived neurotrophic factor (BDNF) serves as a transducer, acting as the link between the antidepressant drug and the neuroplastic changes that result in the improvement of the depressive symptoms. Over the last decade several studies have consistently highlighted BDNF as a key player in antidepressant action. An increase in hippocampal and cortical expression of BDNF mRNA parallels the antidepressant-like response of conventional antidepressants such as SSRIs. Subsequent studies showed that a single bilateral infusion of BDNF into the ventricles or directly into the hippocampus is sufficient to induce a relatively rapid and sustained antidepressant-like effect. Importantly, the antidepressant-like response to conventional antidepressants is attenuated in mice where the BDNF signaling has been disrupted by genetic manipulations. Low dose ketamine, which has been found to induce a rapid antidepressant effect in patients with treatment-resistant depression, is also dependent on increased BDNF signaling. Ketamine transiently increases BDNF translation in hippocampus, leading to enhanced synaptic plasticity and synaptic strength. Ketamine has been shown to increase BDNF translation by blocking NMDA receptor activity at rest, thereby inhibiting calcium influx and subsequently halting eukaryotic elongation factor 2 (eEF2) kinase leading to a desuppression of protein translation, including BDNF translation. The antidepressant-like response of ketamine is abolished in BDNF and TrkB conditional knockout mice, eEF2 kinase knockout mice, in mice carrying the BDNF met/met allele, and by intra-cortical infusions of BDNF-neutralizing antibodies. In summary, current data suggests that conventional antidepressants and ketamine mediate their antidepressant-like effects by increasing BDNF in forebrain regions, in particular the hippocampus, making BDNF an

  3. Treatment of Early-Age Mania: Outcomes for Partial and Nonresponders to Initial Treatment.

    PubMed

    Walkup, John T; Wagner, Karen Dineen; Miller, Leslie; Yenokyan, Gayane; Luby, Joan L; Joshi, Paramjit T; Axelson, David A; Robb, Adelaide; Salpekar, Jay A; Wolf, Dwight; Sanyal, Abanti; Birmaher, Boris; Vitiello, Benedetto; Riddle, Mark A

    2015-12-01

    The Treatment of Early Age Mania (TEAM) study evaluated lithium, risperidone, and divalproex sodium (divalproex) in children with bipolar I disorder who were naive to antimanic medication, or were partial or nonresponders to 1 of 3 study medications. This report evaluates the benefit of either an add-on or a switch of antimanic medications for an 8-week trial period in partial responders and nonresponders, respectively. TEAM is a randomized, controlled trial of individuals (N = 379) aged 6 to 15 years (mean ± SD = 10.2 ± 2.7 years) with DSM-IV bipolar I disorder (mixed or manic phase). Participants (n = 154) in this report were either nonresponders or partial responders to 1 of the 3 study medications. Nonresponders (n = 89) were randomly assigned to 1 of the other 2 antimanic medications and cross-tapered. Partial responders (n = 65) were randomly assigned to 1 of 2 other antimanic medications as an add-on to their initial medication. Adverse event (AE) rates are reported only for the add-on group. Response rate for children switched to risperidone (47.6%) was higher than for those switched to either lithium (12.8%; p = .005; number needed to treat [NNT] = 3; 95% CI = 1.71-9.09) or divalproex (17.2%; p = .03; NNT = 3; 95% CI = 1.79-20.10); response rate for partial responders who added risperidone (53.3%) was higher than for those who added divalproex (0%; p = .0002; NNT = 2; 95% CI = 1.27-3.56) and trended higher for lithium (26.7%; p = .07; NNT = 4). Reported AEs in the add-on group were largely consistent with the known AE profile for the second medication. Weight gain (kg) was observed for all add-on medications: lithium add-on (n = 29 of 30) = 1.66 ± 1.97; risperidone add-on (n = 15 of 15) = 2.8 ± 1.34; divalproex add-on (n = 19 of 20) = 1.42 ± 1.96. There was no evidence at the 5% significance level that the average weight gain was different by study medication for partial responders (p = .07, 1-way analysis of variance

  4. Effectiveness of hygienic-dietary recommendations as enhancers of antidepressant treatment in patients with Depression: Study protocol of a randomized controlled trial

    PubMed Central

    2010-01-01

    Background In recent years some studies have been published supporting the efficacy of light exposure, physical activity, sleep control and a Mediterranean diet pattern on the improvement or prevention of Depression. However, to our knowledge, there have been no studies using all these measures together as an adjuvant antidepressant strategy. Methods Multicenter, randomized, controlled, two arm-parallel, clinical trial. Eighty depressed patients undergoing standard antidepressant treatment will be advised to follow four additional hygienic-dietary recommendations about exercise, diet, sunlight exposure and sleep. Outcome measures will be assessed before and after the 6 month intervention period. Discussion We expect the patients in the active recommendations group to experience a greater improvement in their depressive symptoms. If so, this would be a great support for doctors who might systematically recommend these simple and costless measures, especially in primary care. Trial Registration ISRCTN59506583 PMID:20618920

  5. Immunoglobulin treatment in post-polio syndrome: Identification of responders and non-responders.

    PubMed

    Östlund, Gunilla; Broman, Lisbet; Werhagen, Lars; Borg, Kristian

    2015-09-01

    To define and characterize responders and non-responders in a group of 124 patients with post-polio syndrome who received a single treatment with intravenous immunoglobulin. Open trial, prospective follow-up study. Clinical examination and data from medical records. Short Form 36 (SF-36), Physical Activity Scale for the Elderly (PASE) and visual analogue scale (VAS) measured quality of life, physical activity and intensity of pain, respectively. Data were obtained before treatment and at 6-month follow-up. Two responder groups were identified with the outcome SF-36 Vitality and 3 with Bodily pain, respectively. Forty-five percent were positive-responders, identified before treatment by reduced physical function, muscle atrophy in the lower extremities, higher levels of fatigue and pain, and a VAS pain score above 20. Negative-responders were identified by good physical function and mental health, lesser muscle atrophy in the lower extremities, and low levels of fatigue and pain. Intravenous immunoglobulin is a biological intervention, and therefore it is important to be able to identify responders and non-responders. In order to maximize a positive outcome it is suggested that patients with a high level of fatigue and/or pain and reduced physical function are selected.

  6. Locally advanced rectal cancer: predicting non-responders to neoadjuvant chemoradiotherapy using apparent diffusion coefficient textures.

    PubMed

    Liu, Ming; Lv, Han; Liu, Li-Heng; Yang, Zheng-Han; Jin, Er-Hu; Wang, Zhen-Chang

    2017-07-01

    The purpose of the study is to evaluate whether apparent diffusion coefficient (ADC) textures could identify patient with locally advanced rectal cancer (LARC) who would not respond to neoadjuvant chemoradiotherapy (NCRT). Twenty-six patients who underwent MRI including diffusion-weighted imaging at a 3.0 T system before NCRT were enrolled. Texture analysis of pre-therapy ADC mapping was carried out, and a total of 133 ADC textures as well as routine mean ADC value of the primary tumor were extracted for each patient. Texture parameters and mean ADC were compared between responsive group and non-responsive group. Logistic regression was used to determine the independent predictors for non-responders. Receiver operating characteristic curve (ROC) was performed to evaluate the predictive performance of the significant parameters. Eighteen of the 133 texture parameters significantly differed between responsive and non-responsive groups (p < 0.05). Further, energy variance and SdGa47 were identified as independent predictors for non-responders to NCRT; this logistic model achieved an area under the curve (AUC) of 0.908. Texture analysis based on pre-therapy ADC mapping could potentially be helpful to identify patients with LARC who would not respond to NCRT.

  7. Antidepressant-Induced Sleep Bruxism: Prevalence, Incidence, and Related Factors.

    PubMed

    Uca, Ali Ulvi; Uğuz, Faruk; Kozak, Hasan Hüseyin; Gümüş, Haluk; Aksoy, Fadime; Seyithanoğlu, Abdullah; Kurt, Hatice Güncü

    2015-01-01

    The relationship between sleep bruxism and antidepressant drugs in patients remains unclear. In this study, we aimed to investigate the incidence rate of antidepressant-related bruxism and to examine whether antidepressant use is associated with this adverse effect in the patients. The study sample was gathered from 2 hospitals. A total of 807 patients who met the inclusion criteria were included in the study. The sample was divided into 2 groups: the antidepressant group (n = 506) and the control group (n = 301). Sleep bruxism was established with reports from the study participants on the basis of the International Classification of Sleep Disorders: Diagnosis and Coding Manual Second Edition. The prevalence of bruxism was significantly higher in the antidepressant group (24.3%) than in the control group (15.3%). The incidence of antidepressant-induced bruxism was 14.0%. The antidepressants most associated with bruxism were paroxetine, venlafaxine, and duloxetine. The patients experiencing antidepressant-induced bruxism had higher age compared with those who did not experience this adverse effect. The results of the present study suggest that bruxism is frequently observed in women taking antidepressants and that it seems to be associated with antidepressant use at least in some patients.

  8. New Framework To Diagnose the Direct Disposal of Prescribed Drugs in Wastewater - A Case Study of the Antidepressant Fluoxetine.

    PubMed

    Petrie, Bruce; Youdan, Jane; Barden, Ruth; Kasprzyk-Hordern, Barbara

    2016-04-05

    Intentional or accidental release (direct disposal) of high loads of unused pharmaceuticals into wastewater can go unnoticed. Here, direct disposal of a pharmaceutical drug via the sewer network was identified for the first time using wastewater analysis. An irregularly high load of the antidepressant fluoxetine in raw wastewater (10.5 ± 2.4 g d(-1)) was up to 11 times greater than any other day. National prescription data revealed a predicted daily fluoxetine load for the studied treatment works to be 0.4-1.6 g d(-1). Enantio-selective analysis showed the high load of fluoxetine was present as a racemic mixture, which is typical for fluoxetine in dispensed formulations. As fluoxetine undergoes stereoselective metabolism within the body, a racemic mixture in wastewater suggests a nonconsumed drug was the major contributor of the high load. This was confirmed by its major metabolite norfluoxetine whose load did not increase on this day. Considering the most commonly prescribed formulation of fluoxetine, this increased load accounts for the disposal of ∼915 capsules. Furthermore, as fluoxetine is prescribed as one capsule per day, disposal is unlikely to be at the patient level. It is postulated that direct disposal was from a facility which handles larger quantities of the drug (e.g., a pharmacy).

  9. Influence of external factors on the self-assembly of two structurally related antidepressant drugs: a thermodynamic study

    NASA Astrophysics Data System (ADS)

    Gutiérrez-Pichel, Manuel; Attwood, David; Taboada, Pablo; Mosquera, Víctor

    Apparent molal volumes and adiabatic compressibilities of aqueous solutions of the amphiphilic antidepressant drugs imipramine and desipramine hydrochlorides have been determined from density and ultrasound velocity measurements in the temperature range 288.15-313.15 K in buffered solution of pH 3.0 and 5.5. Critical concentrations for aggregation of these drugs were obtained from inflections on the plots of the sound velocity against drug concentration. Positive deviation from the Debye-Hückel limiting law of the apparent molal volume of imipramine provides evidence of limited association at concentrations below the critical concentration over the temperature range studied. Apparent molal adiabatic compressibilities of the aggregates formed by the drugs, calculated by combining the ultrasound velocity and density data, were typical of those for a stacked aggregate. The critical concentration and energy involved in the aggregation process of these drugs have been evaluated using isothermal titration calorimetry. The solvent-aggregate interactions have been discussed from compressibility and calorimetry data.

  10. Pharmacological Evaluation of Antidepressant-Like Effect of Genistein and Its Combination with Amitriptyline: An Acute and Chronic Study

    PubMed Central

    Gupta, Gaurav; Jia Jia, Tay; Yee Woon, Lim; Kumar Chellappan, Dinesh; Candasamy, Mayuren; Dua, Kamal

    2015-01-01

    The present study was designed to evaluate the acute and chronic antidepressant effect of genistein in combination with amitriptyline in mice. Animals were divided into six groups (n = 6) for treatment with water, genistein, or amitriptyline, either alone or in combination for ten days. Animals were subjected to locomotor activity testing; tail suspension test (TST); and forced swim test (FST) and immobility time was recorded on day one and day ten. Acute treatment of all treatment groups did not significantly reduce the immobility time (p > 0.05). Chronic treatment of combination of genistein (10 mg/kg) and amitriptyline (5 mg/kg and 10 mg/kg) significantly reduced the immobility time as compared to control group (p < 0.001) and was comparable to amitriptyline alone (10 mg/kg). However, no changes in anti-immobility activity in combination of subeffective doses of genistein (5 mg/kg) and amitriptyline (5 mg/kg) were observed. Genistein at its standard dose (10 mg/kg) rendered synergistic effects in combination with subeffective dose of amitriptyline (5 mg/kg) and additive effects in combination with therapeutic dose of amitriptyline (10 mg/kg). PMID:26681936

  11. Convergent Evidence from Mouse and Human Studies Suggests the Involvement of Zinc Finger Protein 326 Gene in Antidepressant Treatment Response

    PubMed Central

    Liou, Ying-Jay; Chen, Chien-Hsiun; Cheng, Chih-Ya; Chen, Shiow-Yi; Chen, Tai-Jui; Yu, Younger W-Y; Nian, Fang-Shin; Tsai, Shih-Jen; Hong, Chen-Jee

    2012-01-01

    Objectives The forced swim test (FST) is a commonly used model to predict antidepressant efficacy. Uncovering the genetic basis of the model may unravel the mechanism of antidepressant treatment. Methods FVB/NJ (FVB) and C57BL/6J (B6) were first identified as the response and non-response strains to fluoxetine (a serotonin-specific reuptake inhibitor antidepressant) treatment in the mouse FST. Simple-interval (SIM) and composite-interval (CIM) mappings were applied to map the quantitative trait loci (QTLs) of the anti-immobility effect of fluoxetine in FST (FSTFLX) in 865 male B6×FVB-F2 mice. The brain mRNA expressions of the gene with the maximum QTL-linkage signal for FSTFLX after the FST were compared between B6 and FVB mice and also compared between fluoxetine and saline treatment. The association of the variants in the human homologue of the mouse FSTFLX-QTL gene with major depressive disorder (MDD) and antidepressant response were investigated in 1080 human subjects (MDD/control = 582/498). Results One linkage signal for FSTFLX-QTL was detected at an intronic SNP (rs6215396) of the mouse Zfp326 gene (maximal CIM-LOD = 9.36). The Zfp326 mRNA expression in the FVB thalamus was significantly down-regulated by fluoxetine in the FST, and the higher FVB-to-B6 Zfp326 mRNA expressions in the frontal cortex, striatum and hypothalamus diminished after fluoxetine treatment. Two coding-synonymous SNPs (rs2816881 and rs10922744) in the human homologue of Zfp326, ZNF326, were significantly associated with the 8-week antidepressant treatment response in the MDD patients (Bonferroni-corrected p = 0.004–0.028). Conclusions The findings suggest the involvement of the Zfp326 and ZNF326 genes in antidepressant treatment response. PMID:22666313

  12. Pattern and predictors of sick leave among users of antidepressants: a Danish retrospective register-based cohort study.

    PubMed

    Gasse, Christiane; Petersen, Liselotte; Chollet, Julien; Saragoussi, Delphine

    2013-12-01

    Depression is associated with work absenteeism, reduced productivity, and significant personal and societal economic burden. We describe patterns and determinants of sick leave among working Danish antidepressant users. Persons starting antidepressant treatment (January 1, 2004 through December 31, 2005) were identified from a representative 25% sample of the Danish population by linking Danish national registries. Inclusion criteria were age 18-64 years, being in the workforce the week prior to the first antidepressant prescription (index prescription, IP), and no antidepressant prescription in the year prior to the IP. Only sick leaves >2 weeks are centrally registered in Denmark and could be assessed. Cox regression analyses identified predictors of sick leave during the year following the IP, based on previous history of sick leave and clinical and socio-demographic baseline characteristics. In the cohort of 25,908 (59.7% women), sick leave prevalence increased from 37.5% (year prior to IP) to 45.3% (year after the IP); 30.7% were on sick leave for >8 weeks. Incidence peaked (35.5% of individuals) the week after the IP. Of persons with sick leave in the year before the IP, 62.7% were on sick leave the first week after the IP, vs 5.7% of those without previous sick leave. Predictors associated with increased risk of sick leave among those without previous sick leave were unemployment, female gender, age 25-54 years, couples with children, and vocational and higher intermediate education (including e.g. teachers and nurses). Reasons for sick leave, sick leaves of less than 14 days and the indications for antidepressant treatment were unknown. Sick leave was prevalent in persons starting new antidepressant use, often lasting >8 weeks. Previous sick leave was the strongest predictor of subsequent sick leave. © 2013 Elsevier B.V. All rights reserved.

  13. The relationship between self-reported mental health and redeemed prescriptions of antidepressants: a register-based cohort study.

    PubMed

    Frandsen, Louise Sjørslev; Villumsen, Line Bilgrav; Hjorth, Cathrine Fonnesbech; Nielsen, Berit Jamie; Ullits, Line Rosenkilde; Torp-Pedersen, Christian; Bøggild, Henrik; Overgaard, Charlotte

    2016-06-07

    Poor mental health is a major problem in most western societies, especially predominant among young adults. However, associations of self-reported poor mental health with subsequent psychiatric or medical treatment are unknown. We examined the relation between self-reported mental health and redeeming prescriptions of antidepressants among three age groups. We analyzed data from 16,233 individuals aged 16 years and over randomly selected to participate in the 2010 North Denmark Region Health Survey completed in February 2010. Mental health was defined according to the Short-Form 12 instrument (SF-12) and dichotomized into poor and good. Outcome data were retrieved from administrative information on redeemed prescriptions of antidepressants between February 2010 and December 2012. Crude cumulative incidence curves were produced to illustrate the probability of redeeming new prescriptions of antidepressants over time. Cox regression analysis was used to estimate risk of redeeming prescriptions of antidepressants when having poor mental health, adjusted for preselected explanatory covariates. Among the young (16-29 years-old), 620 (23 %) participants suffered from poor mental health. Among the adults (30-59 years-old) and elderly (60 years-old or over), 1592 (18 %) participants and 723 (15 %) reported poor mental health, respectively. Overall, women were more likely than men to rate their mental health as poor. For all age groups, there was an increased probability for redeeming prescriptions of antidepressants when having poor mental health. The hazard ratio [HR] for redeeming prescriptions of antidepressants for those reporting poor versus good mental health, adjusted for sex, ethnicity, marital status, education level, occupational status, smoking and physical activity was 3.1 (95 % confidence interval [CI] 2.20-4.29) for young participants. For adults, the HR was 2.3 (95 % CI 1.86-2.78) and for elderly, it was 3.5 (95 % CI 2.66-4.57). Self-reported poor

  14. Pharmacogenetics of antidepressant response: A polygenic approach.

    PubMed

    García-González, Judit; Tansey, Katherine E; Hauser, Joanna; Henigsberg, Neven; Maier, Wolfgang; Mors, Ole; Placentino, Anna; Rietschel, Marcella; Souery, Daniel; Žagar, Tina; Czerski, Piotr M; Jerman, Borut; Buttenschøn, Henriette N; Schulze, Thomas G; Zobel, Astrid; Farmer, Anne; Aitchison, Katherine J; Craig, Ian; McGuffin, Peter; Giupponi, Michel; Perroud, Nader; Bondolfi, Guido; Evans, David; O'Donovan, Michael; Peters, Tim J; Wendland, Jens R; Lewis, Glyn; Kapur, Shitij; Perlis, Roy; Arolt, Volker; Domschke, Katharina; Breen, Gerome; Curtis, Charles; Sang-Hyuk, Lee; Kan, Carol; Newhouse, Stephen; Patel, Hamel; Baune, Bernhard T; Uher, Rudolf; Lewis, Cathryn M; Fabbri, Chiara

    2017-04-03

    Major depressive disorder (MDD) has a high personal and socio-economic burden and >60% of patients fail to achieve remission with the first antidepressant. The biological mechanisms behind antidepressant response are only partially known but genetic factors play a relevant role. A combined predictor across genetic variants may be useful to investigate this complex trait. Polygenic risk scores (PRS) were used to estimate multi-allelic contribution to: 1) antidepressant efficacy; 2) its overlap with MDD and schizophrenia. We constructed PRS and tested whether these predicted symptom improvement or remission from the GENDEP study (n=736) to the STAR*D study (n=1409) and vice-versa, including the whole sample or only patients treated with escitalopram or citalopram. Using summary statistics from Psychiatric Genomics Consortium for MDD and schizophrenia, we tested whether PRS from these disorders predicted symptom improvement in GENDEP, STAR*D, and five further studies (n=3756). No significant prediction of antidepressant efficacy was obtained from PRS in GENDEP/STAR*D but this analysis might have been underpowered. There was no evidence of overlap in the genetics of antidepressant response with either MDD or schizophrenia, either in individual studies or a meta-analysis. Stratifying by antidepressant did not alter the results. We identified no significant predictive effect using PRS between pharmacogenetic studies. The genetic liability to MDD or schizophrenia did not predict response to antidepressants, suggesting differences between the genetic component of depression and treatment response. Larger or more homogeneous studies will be necessary to obtain a polygenic predictor of antidepressant response. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. A possible mechanism of the nucleus accumbens and ventral pallidum 5-HT1B receptors underlying the antidepressant action of ketamine: a PET study with macaques

    PubMed Central

    Yamanaka, H; Yokoyama, C; Mizuma, H; Kurai, S; Finnema, S J; Halldin, C; Doi, H; Onoe, H

    2014-01-01

    Ketamine is a unique anesthetic reagent known to produce various psychotic symptoms. Ketamine has recently been reported to elicit a long-lasting antidepressant effect in patients with major depression. Although recent studies provide insight into the molecular mechanisms of the effects of ketamine, the antidepressant mechanism has not been fully elucidated. To understand the involvement of the brain serotonergic system in the actions of ketamine, we performed a positron emission tomography (PET) study on non-human primates. Four rhesus monkeys underwent PET studies with two serotonin (5-HT)-related PET radioligands, [11C]AZ10419369 and [11C]DASB, which are highly selective for the 5-HT1B receptor and serotonin transporter (SERT), respectively. Voxel-based analysis using standardized brain images revealed that ketamine administration significantly increased 5-HT1B receptor binding in the nucleus accumbens and ventral pallidum, whereas it significantly reduced SERT binding in these brain regions. Fenfluramine, a 5-HT releaser, significantly decreased 5-HT1B receptor binding, but no additional effect was observed when it was administered with ketamine. Furthermore, pretreatment with 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline (NBQX), a potent antagonist of the glutamate α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor, blocked the action of ketamine on the 5-HT1B receptor but not SERT binding. This indicates the involvement of AMPA receptor activation in ketamine-induced alterations of 5-HT1B receptor binding. Because NBQX is known to block the antidepressant effect of ketamine in rodents, alterations in the serotonergic neurotransmission, particularly upregulation of postsynaptic 5-HT1B receptors in the nucleus accumbens and ventral pallidum may be critically involved in the antidepressant action of ketamine. PMID:24399045

  16. The relation of antipsychotic and antidepressant medication with baseline symptoms and symptom progression: A naturalistic study of the North American Prodrome Longitudinal Sample

    PubMed Central

    Walker, Elaine F.; Cornblatt, Barbara A.; Addington, Jean; Cadenhead, Kristin S.; Cannon, Tyrone D.; McGlashan, Thomas H.; Perkins, Diana O.; Seidman, Larry J.; Tsuang, Ming T.; Woods, Scott W.; Heinssen, Robert

    2009-01-01

    A substantial number of patients who meet criteria for a prodromal syndrome for first psychosis are treated with antipsychotic and/or antidepressant medications. There is suggestive evidence that both classes of medication may reduce prodromal symptoms. This longitudinal study examined the relation of antipsychotic and antidepressant medication with prodromal symptom severity at baseline and 6-month follow-up. Participants met Structured Interview for Prodromal Syndromes (SIPS) criteria for the prodrome, and were evaluated at eight centers as part of the North American Prodrome Longitudinal Study (NAPLS).Symptom ratings (positive, negative, disorganized and general) and data on antipsychotics, SSRIs, and other antidepressant medications were obtained at baseline and 6-month follow-up. Analyses revealed that all symptom dimensions declined in severity over time, but there were differences in the magnitude of the decline as a function of antipsychotic medication. Those never on antipsychotics showed less reduction in positive and disorganized symptoms over time. SSRIs and other antidepressants were not linked with declines in symptom severity. Consistent with findings from small-sample, clinical trials, the present results suggest that atypical antipsychotics may be effective in reducing the severity of attenuated positive symptoms associated with the prodrome to psychotic disorders. Limitations of the present study are noted, including the fact that it is not a randomized trial, and data on duration and dosage of medication and 2-year follow-up were not available for most participants. The results are discussed in light of the relative risks and benefits of preventive interventions, both medication and cognitive therapies, and the importance of future clinical trials. PMID:19709859

  17. Antidepressant Activity of Brahmi in Albino Mice

    PubMed Central

    Kadali, SLDV Ramana Murty; M.C., Das; Rao A.S.R., Srinivasa; Sri G, Karuna

    2014-01-01

    Context: In traditional system of medicine brahmi has been used to enhance memory. Recently it has been reported to have action in psychiatric disorders. With these backgrounds the work has been undertaken to study antidepressant activity of brahmi in albino mice. Aim: To evaluate antidepressant activity of brahmi in experimental models. Materials and Methods: The antidepressant activity was studied in albino mice using forced swimming test (FST), tail suspension test (TST) and shock induced depression (SID). Imipramine (10mg/kg), fluoxetine (30mg/kg) were used as standard drugs and brahmi (10, 20, 30mg/kg) was used as test drug. Results: Brahmi exhibited significant decrease in duration of immobility in FST and reduced the shock induced decrease in activity in SID models. It didn’t show any activity in the TST model. Conclusion: Brahmi has shown antidepressant activity in FST and SID. PMID:24783074

  18. Chemistry, Pharmacology, and Behavioral Studies Identify Chiral Cyclopropanes as Selective α4β2- Nicotinic Acetylcholine Receptor Partial Agonists Exhibiting an Antidepressant Profile. Part II

    PubMed Central

    Zhang, Han-Kun; Yu, Li-Fang; Eaton, J. Brek; Whiteaker, Paul; Onajole, Oluseye K.; Hanania, Taleen; Brunner, Daniela; Lukas, Ronald J.; Kozikowski, Alan P.

    2013-01-01

    A 3-pyridyl ether scaffold bearing a cyclopropane-containing side chain was recently identified in our efforts to create novel antidepressants that act as partial agonists at α4β2-nicotinic acetylcholine receptors. In this study, a systematic structure-activity relationship investigation was carried out on both the azetidine moiety present in compound 3 and its right-hand side chain, thereby discovering a variety of novel nicotinic ligands that retain bioactivity and feature improved chemical stability. The most promising compounds 24, 26, and 30 demonstrated comparable or enhanced pharmacological profiles compared to the parent compound 4, and the N-methylpyrrolidine analogue 26 also exhibited robust antidepressant-like efficacy in the mouse forced swim test. The favorable ADMET profile and chemical stability of 26 further indicate this compound to be a promising lead as a drug candidate warranting further advancement down the drug discovery pipeline. PMID:23734673

  19. Chemistry, pharmacology, and behavioral studies identify chiral cyclopropanes as selective α4β2-nicotinic acetylcholine receptor partial agonists exhibiting an antidepressant profile. Part II.

    PubMed

    Zhang, Han-Kun; Yu, Li-Fang; Eaton, J Brek; Whiteaker, Paul; Onajole, Oluseye K; Hanania, Taleen; Brunner, Daniela; Lukas, Ronald J; Kozikowski, Alan P

    2013-07-11

    A 3-pyridyl ether scaffold bearing a cyclopropane-containing side chain was recently identified in our efforts to create novel antidepressants that act as partial agonists at α4β2-nicotinic acetylcholine receptors. In this study, a systematic structure-activity relationship investigation was carried out on both the azetidine moiety present in compound 3 and its right-hand side chain, thereby discovering a variety of novel nicotinic ligands that retain bioactivity and feature improved chemical stability. The most promising compounds, 24, 26, and 30, demonstrated comparable or enhanced pharmacological profiles compared to the parent compound 4, and the N-methylpyrrolidine analogue 26 also exhibited robust antidepressant-like efficacy in the mouse forced swim test. The favorable ADMET profile and chemical stability of 26 further indicate this compound to be a promising lead as a drug candidate warranting further advancement down the drug discovery pipeline.

  20. Depression, anxiety, antidepressant use, and cardiovascular disease among Hispanic men and women of different national backgrounds: results from the Hispanic Community Health Study/Study of Latinos.

    PubMed

    Wassertheil-Smoller, Sylvia; Arredondo, Elva M; Cai, JianWen; Castaneda, Sheila F; Choca, James P; Gallo, Linda C; Jung, Molly; LaVange, Lisa M; Lee-Rey, Elizabeth T; Mosley, Thomas; Penedo, Frank J; Santistaban, Daniel A; Zee, Phyllis C

    2014-11-01

    To describe prevalence and relationships to cardiovascular morbidity of depression, anxiety, and medication use among Hispanic/Latinos of different ethnic backgrounds. Cross-sectional analysis of 15,864 men and women aged 18 to 74 years in the population-based Hispanic Community Health Study/Study of Latinos. Depressive and anxiety symptoms were assessed with shortened Center for Epidemiological Studies Depression Scale and Spielberger Trait Anxiety Scale. Prevalence of high depressive symptoms ranged from low of 22.3% (95% confidence interval [CI], 20.4-24.3) to high of 38.0% (95% CI, 35.2-41.0) among those of Mexican or Puerto Rican background, respectively. Adjusted odds ratios for depression rose monotonically with number of cardiovascular disease (CVD) risk factor from 1.46 (95% CI, 1.18-1.75) for those with one risk factors to 4.36 (95% CI, 2.47-7.70) for those with five risk factors. Antidepressant medication was used by 5% with striking differences between those with and without history of CVD (15.4% and 4.6%, respectively) and between insured (8.2%) and uninsured (1.8%). Among US Hispanics/Latinos, high depression and anxiety symptoms varied nearly twofold by Hispanic background and sex, history of CVD, and increasing number of CVD risk factors. Antidepressant medication use was lower than in the general population, suggesting under treatment especially among those who had no health insurance. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Combination treatment of fingolimod with antidepressants in relapsing–remitting multiple sclerosis patients with depression: a multicentre, open-label study – REGAIN

    PubMed Central

    Bayas, Antonios; Schuh, Katrin; Baier, Monika; Vormfelde, Stefan Viktor; Koppai-Reiner, Joachim

    2016-01-01

    Objectives: Approximately one in two patients with multiple sclerosis (MS) suffer from comorbid depression. The primary objective of this study was to evaluate the safety and tolerability of fingolimod and antidepressant combination in relapsing–remitting MS patients with mild-to-moderate depression. Efficacy outcome variables were quality of life (QoL), fatigue, disability and depression. Methods: Patients received open-label fingolimod 0.5 mg over 2 weeks, followed by fingolimod plus citalopram (40 mg), fluoxetine (40 mg) or venlafaxine (150 mg) over 16 weeks. The antidepressant was selected at the physician’s discretion. Results: In total, 54 patients were recruited at 25 centres across Germany. No new safety signals (including cardiac) emerged compared with previous clinical studies. Adverse events (mostly mild-to-moderate) were reported in 43 patients. A total of three patients had serious adverse events and 10 discontinued the study. QoL (mean [95% confidence interval]) improved by 2.2 (−3.3, −1.2; Patient Reported Indices for MS questionnaire), fatigue by 8.2 (−13.1, −3.3; modified Fatigue Impact Scale) and depression by 6.3 (−8.4, −4.2; Hamilton Depression Scale) points. However, the results must be interpreted cautiously owing to limited patient numbers. Conclusions: Combination of fingolimod with antidepressant medication showed no unexpected safety signals. Patient-reported outcomes (QoL, disability, fatigue and depression) remained stable or improved. PMID:27582893

  2. Pharmacogenetic analysis of genes implicated in rodent models of antidepressant response: association of TREK1 and treatment resistance in the STAR(*)D study.

    PubMed

    Perlis, Roy H; Moorjani, Priya; Fagerness, Jesen; Purcell, Shaun; Trivedi, Madhukar H; Fava, Maurizio; Rush, A John; Smoller, Jordan W

    2008-11-01

    Recent rodent models of antidepressant response implicate a novel set of genes in mechanisms of antidepressant action. The authors examined variants in four such genes (KCNK2 (TREK1), SLC18A2 (VMAT2), S100A10, and HDAC5) for association with remission in a large effectiveness trial of antidepressant treatments. Subjects were drawn from the Sequenced Treatment Alternatives to Relieve Depression (STAR(*)D) study, a multicenter, prospective, effectiveness trial in major depressive disorder (MDD). Outpatients with nonpsychotic MDD were initially treated with citalopram for up to 14 weeks; those who did not remit with citalopram were sequentially randomized to a series of next-step treatments, each for up to 12 weeks. Single-nucleotide polymorphisms in four genes were examined for association with remission, defined as a clinician-rated Quick Inventory of Depressive Symptomatology (QIDS-C(16)) score < or =5. Of 1554 participants for whom DNA was available, 565 (36%) reached remission with citalopram treatment. No association with any of the four genes was identified. However, among the 751 who entered next-step treatment, variants in KCNK2 were associated with treatment response (Bonferroni-corrected, gene-based empirical p<0.001). In follow-up analyses, KCNK2 was also associated with effects of similar magnitude for third-step treatment among those with unsatisfactory benefit to both citalopram and one next-step pharmacotherapy (n=225). These findings indicate that genetic variation in KCNK2 may identify individuals at risk for treatment resistance. More broadly, they indicate the utility of animal models in identifying genes for pharmacogenetic studies of antidepressant response.

  3. Prediction of antidepressant response to venlafaxine by a combination of early response assessment and therapeutic drug monitoring.

    PubMed

    Stamm, T J; Becker, D; Sondergeld, L M; Wiethoff, K; Hiemke, C; O'Malley, G; Ricken, R; Bauer, M; Adli, M

    2014-07-01

    Early assessment of a therapeutic response is a central goal in antidepressant treatment. The present study examined the potential for therapeutic drug monitoring and symptom rating to predict venlafaxine treatment efficacy (measured by overall patient response and remission). 88 patients were uptitrated homogenously to 225 mg/day venlafaxine. Serum concentrations of venlafaxine (VEN) and its active metabolite O-desmethylvenlafaxine (ODV) were measured at week 2. Continuous psychopathometric ratings were measured for up to 6 weeks by independent study raters. An early improvement was significantly more common in venlafaxine responders than non-responders (χ(2); p=0.007). While ODV serum levels were significantly higher in responders (t test; p=0.006), VEN serum levels, sum level of VEN+ODV and the ratio of ODV/VEN levels were not. Moreover, patients who showed an early response combined with an ODV serum level above the median of 222 ng/mL were significantly more likely to achieve full response (binary logistic model; p<0.01). Sensitivity (84% for early response) and specificity (81% for combination of early response and therapeutic drug monitoring) were sufficient to qualify as a reasonable screening instrument. Our results indicate that early improvement and ODV serum concentration are predictive of therapeutic outcome and can thus be used to guide use of the antidepressant venlafaxine. © Georg Thieme Verlag KG Stuttgart · New York.

  4. LC/QTOF profile and preliminary stability studies of an enriched flavonoid fraction of Cecropia pachystachya Trécul leaves with potential antidepressant-like activity.

    PubMed

    Ortmann, Caroline Flach; Abelaira, Helena Mendes; Réus, Gislaine Zilli; Ignácio, Zuleide Maria; Chaves, Vitor Clasen; Dos Santos, Talitha Caldas; de Carvalho, Pâmela; Carlessi, Anelise Scussel; Bruchchen, Livia; Danielski, Lucineia G; Cardoso, Simone Gonçalves; de Campos, Angela Machado; Petronilho, Fabricia; Rebelo, Joyce; Dos Santos Morais, Meline Oliveira; Vuolo, Francieli; Dal-Pizzol, Felipe; Streck, Emilio Luiz; Quevedo, João; Reginatto, Flávio Henrique

    2017-03-31

    There is increasing interest in natural antioxidants that are candidates for the prevention of brain damage occurring in major depressive disorders. Cecropia pachystachya is a tropical tree species of Central and South America and a rich source of polyphenols, particularly flavonoids. The aim of this study was to characterize the flavonoid profile of an enriched flavonoid fraction of C. pachystachya (EFF-Cp) and evaluate the antidepressant-like effects of its acute administration in behavior, cytokine levels, oxidative stress and energy metabolism parameters. The EFF-Cp chemical characterization was performed by HPLC/DAD and LC/QTOF. The antidepressant-like effects were performed by the forced swimming test, splash test and open field test. EFF-Cp revealed 15 flavonoids, including seven new glycosyl flavonoids for C. pachystachya. Quantitatively, EFF-Cp showed isoorientin (43.46 mg/g), orientin (23.42 mg/g) and isovitexin (17.45 mg/g) as major C-glycosyl flavonoids. In addition, EFF-Cp at doses 50 and 100 mg/kg reduced the immobility time in the forced swimming test, without changing the locomotor activity and grooming time. In addition, EFF-Cp was able to prevent the oxidative damage in some brain areas. In conclusion, the results of this study suggest that EFF-Cp exerts antidepressant-like effects with its antioxidant properties. Copyright © 2017 John Wiley & Sons, Ltd.

  5. Combining Antidepressants in Acute Treatment of Depression: A Meta-Analysis of 38 Studies Including 4511 Patients

    PubMed Central

    Henssler, Jonathan; Bschor, Tom

    2016-01-01

    Objective: Combining antidepressants (ADs) for therapy of acute depression is frequently employed, but randomized studies have yielded conflicting results. We conducted a systematic review and meta-analysis aimed at determining efficacy and tolerability of combination therapy. Methods: MEDLINE, Embase, PsycINFO, and CENTRAL databases were systematically searched through March 2014 for controlled studies comparing combinations of ADs with AD monotherapy in adult patients suffering from acute depression. The prespecified primary outcome was standardized mean difference (SMD), secondary outcomes were response, remission, and dropouts. Results: Among 8688 articles screened, 38 studies were eligible, including 4511 patients. Combination treatment was statistically, significantly superior to monotherapy (SMD 0.29; 95% CI 0.16 to 0.42). During monotherapy, slightly fewer patients dropped out due to adverse events (OR 0.90; 95% CI 0.53 to 1.53). Studies were heterogeneous (I2 = 63%), and there was indication of moderate publication bias (fail-safe N for an effect of 0.1:44), but results remained robust across prespecified secondary outcomes and subgroups, including analyses restricted to randomized controlled trials and low risk of bias studies. Meta-regression revealed an association of SMD with difference in imipramine-equivalent dose. Combining a reuptake inhibitor with an antagonist of presynaptic α2-autoreceptors was superior to other combinations. Conclusion: Combining ADs seems to be superior to monotherapy with only slightly more patients dropping out. Combining a reuptake inhibitor with an antagonist of presynaptic α2-autoreceptors seems to be significantly more effective than other combinations. Overall, our search revealed a dearth of well-designed studies. PMID:27582451

  6. Antidepressant effects of ketamine: mechanisms underlying fast-acting novel antidepressants

    PubMed Central

    Browne, Caroline A.; Lucki, Irwin

    2013-01-01

    Newer antidepressants are needed for the many individuals with major depressive disorder (MDD) that do not respond adequately to treatment and because of a delay of weeks before the emergence of therapeutic effects. Recent evidence from clinical trials shows that the NMDA antagonist ketamine is a revolutionary novel antidepressant because it acts rapidly and is effective for treatment-resistant patients. A single infusion of ketamine alleviates depressive symptoms in treatment-resistant depressed patients within hours and these effects may be sustained for up to 2 weeks. Although the discovery of ketamine's effects has reshaped drug discovery for antidepressants, the psychotomimetic properties of this compound limit the use of this therapy to the most severely ill patients. In order to develop additional antidepressants like ketamine, adequate preclinical behavioral screening paradigms for fast-acting antidepressants need to be established and used to identify the underlying neural mechanisms. This review examines the preclinical literature attempting to model the antidepressant-like effects of ketamine. Acute administration of ketamine has produced effects in behavioral screens for antidepressants like the forced swim test, novelty suppression of feeding and in rodent models for depression. Protracted behavioral effects of ketamine have been reported to appear after a single treatment that last for days. This temporal pattern is similar to its clinical effects and may serve as a new animal paradigm for rapid antidepressant effects in humans. In addition, protracted changes in molecules mediating synaptic plasticity have been implicated in mediating the antidepressant-like behavioral effects of ketamine. Current preclinical studies are examining compounds with more specific pharmacological effects at glutamate receptors and synapses in order to develop additional rapidly acting antidepressants without the hallucinogenic side effects or abuse potential of ketamine

  7. Antidepressant drugs and infectious disease.

    PubMed

    Howland, Robert H

    2013-07-01

    Clostridium difficile (C.difficile) infection (CDI) is a common and clinically significant cause of diarrhea associated with the use of antibiotic drugs. Two observational studies have suggested that antidepressant drug use is associated with an increased risk of developing CDI. Because of the potential public health significance of this finding, this article critically evaluates the methodology of these studies and provides evidence to question the plausibility and validity of this finding. The safety of antidepressant and other psychotropic drugs should not be taken for granted, but studies that receive media attention may cause harm if their findings are not valid and they result in a reluctance to use these drugs for treating serious mental disorders.

  8. [Are antidepressants really effective?].

    PubMed

    Ammendola, S; Kornreich, C

    2015-01-01

    Antidepressants are widely used for a long time and it is estimated that about 10 % of the belgian population is taking some of them each year. However, there are important controversies about their real efficacy. We review successively arguments for and against their efficacy. On the one hand, meta-analysis have shown no big efficacy differences between antidepressants and placebo. On the other hand, those meta-analysis have been criticized for their methodology. Animal models show a real effect of antidepressants on the brain and clinical observations, such as an impact on suicide prevention, the possibility of induced manic switch, and an efficacy on anxiety disorders are in favour of a real efficacy. Given our current state of knowledge about them it seems appropriate to continue to use anti-depressants in the treatment of depressive patients.

  9. Treatment of Fibromyalgia with Antidepressants

    PubMed Central

    O'Malley, Patrick G; Balden, Erin; Tomkins, Glen; Santoro, James; Kroenke, Kurt; Jackson, Jeffrey L

    2000-01-01

    BACKGROUND Fibromyalgia is a common, poorly understood musculoskeletal pain syndrome with limited therapeutic options. OBJECTIVE To systematically review the efficacy of antidepressants in the treatment of fibromyalgia and examine whether this effect was independent of depression. DESIGN Meta-analysis of English-language, randomized, placebo-controlled trials. Studies were obtained from searching medline, embase, and psyclit(1966-1999), the Cochrane Library, unpublished literature, and bibliographies. We performed independent duplicate review of each study for both inclusion and data extraction. MAIN RESULTS Sixteen randomized, placebo-controlled trials were identified, of which 13 were appropriate for data extraction. There were 3 classes of antidepressants evaluated: tricyclics (9 trials), selective serotonin reuptake inhibitors (3 trials), and S-adenosylmethionine (2 trials). Overall, the quality of the studies was good (mean score 5.6, scale 0-8). The odds ratio for improvement with therapy was 4.2 (95% confidence interval [95% CI], 2.6 to 6.8). The pooled risk difference for these studies was 0.25 (95% CI, 0.16 to 0.34), which calculates to 4 (95% CI, 2.9 to 6.3) individuals needing treatment for 1 patient to experience symptom improvement. When the effect on individual symptoms was combined, antidepressants improved sleep, fatigue, pain, and well-being, but not trigger points. In the 5 studies where there was adequate assessment for an effect independent of depression, only 1 study found a correlation between symptom improvement and depression scores. Outcomes were not affected by class of agent or quality score using meta-regression. CONCLUSION Antidepressants are efficacious in treating many of the symptoms of fibromyalgia. Patients were more than 4 times as likely to report overall improvement, and reported moderate reductions in individual symptoms, particularly pain. Whether this effect is independent of depression needs further study. PMID:11029681

  10. The Effect of Nonrespondents on a Self-Administered Mail Survey.

    ERIC Educational Resources Information Center

    Krushat, W. Mark; Molnar, John I.

    1993-01-01

    After a mailed questionnaire and two follow-ups, hard-core survey nonrespondents were contacted to ask why they had not responded and what they would have answered had they responded. Results from 28 subjects indicate that efforts to pursue nonrespondents may be unnecessary, because bias resulting from nonresponse appeared minimal. (SLD)

  11. The Functional Study of a Chinese Herbal Compounded Antidepressant Medicine – Jie Yu Chu Fan Capsule on Chronic Unpredictable Mild Stress Mouse Model

    PubMed Central

    Ding, Lingling; Zhang, Xiaoyu; Guo, Hongliang; Yuan, Junliang; Li, Shujuan; Hu, Wenli; Golden, Teresa; Wu, Ning

    2015-01-01

    Jie Yu Chu Fan capsule (JYCF) is a new compounded Chinese herbal medicine for the treatment of depression. The present study was designed to explore the antidepressant effects and the possible mechanisms of JYCF by using chronic unpredictable mild stress (CUMS) mouse model and comparing results to that of fluoxetine. Behavioral tests including an open field test, sucrose preference test and forced swim test were performed to evaluate the antidepressant effects of JYCF. The concentrations of monoamine neurotransmitters and metabolic products including norepinephrine (NE), 5-hydroxytryptamine (5-HT), dopamine (DA), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the cerebral cortex and hippocampus of mice were determined by means of high performance liquid chromatography with electrochemical detection (HPLC-EC). The results show that a successful mouse CUMS model was established through 5 weeks of continuous unpredictable stimulation, as indicated by the significant decrease in sucrose preference and locomotor activity and increase in immobility time in the forced swim test. Chronic treatment of JYCF (1.25, 2.5 and 5 g/kg) and fluoxetine (20mg/kg) significantly reversed the CUMS-induced behavioral abnormalities. JYCF (1.25, 2.5 and 5 g/kg) significantly increased NE in CUMS mouse prefrontal cortex (P < 0.01, P < 0.01, P < 0.05 respectively) and 5-HT in hippocampus (P < 0.05). In summary, our findings suggest that JYCF exerts comparable antidepressant-like effects to that of fluoxetine in CUMS mice. Besides, the antidepressant-like effect of JYCF is mediated by the increase of monoaminergic transmitters including 5-HT and NE. PMID:26186537

  12. Do antidepressants increase the risk of mania and bipolar disorder in people with depression? A retrospective electronic case register cohort study

    PubMed Central

    Reiss, Peter; Shetty, Hitesh; Broadbent, Matthew; Stewart, Robert; McGuire, Philip; Taylor, Matthew

    2015-01-01

    Objectives To investigate the association between antidepressant therapy and the later onset of mania/bipolar disorder. Design Retrospective cohort study using an anonymised electronic health record case register. Setting South London and Maudsley National Health Service (NHS) Trust (SLaM), a large provider of inpatient and community mental healthcare in the UK. Participants 21 012 adults presenting to SLaM between 1 April 2006 and 31 March 2013 with unipolar depression. Exposure Prior antidepressant therapy recorded in electronic health records. Main outcome measure Time to subsequent diagnosis of mania or bipolar disorder from date of diagnosis of unipolar depression, censored at 31 March 2014. Methods Multivariable Cox regression analysis with age and gender as covariates. Results The overall incidence rate of mania/bipolar disorder was 10.9 per 1000 person-years. The peak incidence of mania/bipolar disorder incidence was seen in patients aged between 26 and 35 years (12.3 per 1000 person-years). Prior antidepressant treatment was associated with an increased incidence of mania/bipolar disorder ranging from 13.1 to 19.1 per 1000 person-years. Multivariable analysis indicated a significant association with selective serotonin reuptake inhibitors (HR 1.34, 95% CI 1.18 to 1.52) and venlafaxine (1.35, 1.07 to 1.70). Conclusions In people with unipolar depression, antidepressant treatment is associated with an increased risk of subsequent mania/bipolar disorder. These findings highlight the importance of considering risk factors for mania when treating people with depression. PMID:26667012

  13. Therapeutic drug monitoring for antidepressant drug treatment.

    PubMed

    Ostad Haji, Elnaz; Hiemke, Christoph; Pfuhlmann, Bruno

    2012-01-01

    The aim of antidepressant drug treatment is to produce remission without causing adverse effects during the acute phase of the illness and to prevent relapses or recurrences during continuation or maintenance therapy. To achieve these goals, drug choice and dosage must be optimized for each patient individually. Therapeutic drug monitoring (TDM), which is based on the assumption that clinical effects correlate better with blood levels than doses, can be helpful. When using tricyclic antidepressant drugs TDM enhances safety and efficacy. For newer antidepressant drugs, however, it is a matter of debate to which extend TDM can have beneficial effects. For many antidepressants there exist carefully designed studies concerning the relationship between plasma concentration and clinical effects that allow the definition of recommended therapeutic ranges of the plasma concentration. In some drugs however, concentration-effect studies are lacking so far, but target ranges resulting from clinically relevant plasma concentrations or from pharmacokinetic studies could be provided. During the last years, knowledge on therapeutic references ranges in blood towards TDM guided treatment has markedly improved for new antidepressant drugs, and many specific indications have been defined for useful TDM. Recently published guidelines describe the best practice of TDM for neuropsychiatric drugs. The aim of this review is to summarize the current status of TDM for antidepressant drugs and discuss the literature with regard to response optimization, pharmacovigilance and economic benefits and with regard to needs for further research.

  14. Associations Between Personality Traits and Adherence to Antidepressants Assessed Through Self-Report, Electronic Monitoring, and Pharmacy Dispensing Data: A Pilot Study.

    PubMed

    Wouters, Hans; Amin, Darya F H; Taxis, Katja; Heerdink, Eibert R; Egberts, Antoine C G; Gardarsdottir, Helga

    2016-10-01

    Treatment with antidepressants is often compromised by substantial nonadherence. To understand nonadherence, specific medication-related behaviors and beliefs have been studied, but less is known about broader and temporally stable personality "traits." Furthermore, adherence has often been assessed by a single method. Hence, we investigated associations between the Big Five personality traits and adherence assessed by self-report, electronic drug use monitoring, and dispensing data. Using the Big Five Inventory, we assessed the personality traits "openness," "conscientiousness," "extraversion," "agreeableness," and "neuroticism" of patients treated with antidepressants who were invited through community pharmacies. Self-reported adherence was assessed with the Medication Adherence Rating Scale (score >24), electronic monitoring with medication event monitoring system (MEMS) devices (therapy days missed ≤ 10% and < 4 consecutive days missed), and dispensing data (medication possession ratio ≥ 80%). One hundred four women and 33 men participated (mean age, 51; standard deviation, 14). Paroxetine was most frequently prescribed (N = 53, 38%). Logistic regression analysis revealed that of the personality traits, the third and fourth quartiles of "conscientiousness" were associated with better self-reported adherence (odds ratio, 3.63; 95% confidence interval, 1.34-9.86 and odds ratio, 2.97; 95% confidence interval, 1.09-8.08; P ≤ 0.05). No relationships were found between personality traits and adherence assessed through electronic drug use monitoring or dispensing data. We therefore conclude that adherence to antidepressant therapy seems to be largely unrelated to personality traits.

  15. Antidepressants, antimicrobials or both? Gut microbiota dysbiosis in depression and possible implications of the antimicrobial effects of antidepressant drugs for antidepressant effectiveness.

    PubMed

    Macedo, Danielle; Filho, Adriano José Maia Chaves; Soares de Sousa, Caren Nádia; Quevedo, João; Barichello, Tatiana; Júnior, Hélio Vitoriano Nobre; Freitas de Lucena, David

    2017-01-15

    The first drug repurposed for the treatment of depression was the tuberculostatic iproniazid. At present, drugs belonging to new classes of antidepressants still have antimicrobial effects. Dysbiosis of gut microbiota was implicated in the development or exacerbation of mental disorders, such as major depressive disorder (MDD). Based on the current interest in the gut-brain axis, the focus of this narrative review is to compile the available studies regarding the influences of gut microbiota in behavior and depression and to show the antimicrobial effect of antidepressant drugs. A discussion regarding the possible contribution of the antimicrobial effect of antidepressant drugs to its effectiveness/resistance is included. The search included relevant articles from PubMed, SciELO, LILACS, PsycINFO, and ISI Web of Knowledge. MDD is associated with changes in gut permeability and microbiota composition. In this respect, antidepressant drugs present antimicrobial effects that could also be related to the effectiveness of these drugs for MDD treatment. Conversely, some antimicrobials present antidepressant effects. Both antidepressants and antimicrobials present neuroprotective/antidepressant and antimicrobial effects. Further studies are needed to evaluate the participation of antimicrobial mechanisms of antidepressants in MDD treatment as well as to determine the contribution of this effect to antidepressant resistance. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. The Efficacy and Safety of Clonazepam in Patients with Anxiety Disorder Taking Newer Antidepressants: A Multicenter Naturalistic Study

    PubMed Central

    Wang, Sheng-Min; Kim, Jung-Bum; Sakong, Jeong Kyu; Suh, Ho-Suk; Oh, Kang Seob; Woo, Jong-Min; Yoo, Sang-Woo; Lee, Sang Min; Lee, Sang-Yeol; Lim, Se-Won; Cho, Seong Jin; Chee, Ik-Seung; Chae, Jeong-Ho; Hong, Jin Pyo; Lee, Kyoung-Uk

    2016-01-01

    Objective This study compared the efficacy and tolerability of clonazepam with other benzodiazepines in patients with anxiety disorders. Methods Inclusion criteria were as follows: age >20 years, diagnosis of anxiety disorder according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition, text revision (DSM-IV-TR) criteria, taking only one type of antidepressant, and prescribed one of three oral benzodiazepines (alprazolam, clonazepam, or lorazepam). At baseline and week 6, clinical benefit was evaluated using the Clinical Global Impression-Severity Scale (CGI-S), Clinical Global Impression-Anxiety Scale (CGI-anxiety), and Clinical Global Impression-Sleep Scale (CGI-sleep). Results Among 180 patients, no differences in demographic characteristics among the three benzodiazepine groups were noted. After six weeks of treatment, all benzodiazepine groups showed significant improvements in CGI-S, CGI-anxiety, and CGI-sleep scores (p<0.001). There were no differences in mean changes in CGI-S, CGI-anxiety and CGI-sleep among the three benzodiazepine groups. The incidence of side effects was significantly lower in the clonazepam group than with the other benzodiazepines. The incidences of adverse events for the clonazepam, alprazolam, and lorazepam groups were 26.7% (n=20), 48.4% (n=31), and 43.9% (n=18), respectively. Conclusion The present study suggests that clonazepam is as efficacious as other benzodiazepines for the treatment of various anxiety disorders. Furthermore, the safety profile of clonazepam was superior to the other benzodiazepines in this study. PMID:27121429

  17. Use of SSRI and SNRI Antidepressants during Pregnancy: A Population-Based Study from Denmark, Iceland, Norway and Sweden

    PubMed Central

    Zoega, Helga; Kieler, Helle; Nørgaard, Mette; Furu, Kari; Valdimarsdottir, Unnur; Brandt, Lena; Haglund, Bengt

    2015-01-01

    Background The purpose was to describe utilization of selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs), including trends in prevalence, characteristics of users, drug switching and changes in prescribed doses in a large group of pregnant women across four Nordic countries. Methods A drug utilization study based on linked individual-level data from the nationwide prescription- and medical birth registers in Denmark, Iceland, Norway and Sweden. The study population comprised all pregnancies in these countries, resulting in a live birth or stillbirth after gestational week 22 from January 1st 2008 to December 31st 2012 (N = 1 162 470). In addition to the main study drugs SSRIs and SNRIs, we included (concurrent) use of other antidepressants, antipsychotics, anxiolytics and hypnotics. Results A total of 38 219 (3.3%) pregnancies were exposed to SSRIs and 5 634 (0.5%) to SNRIs. Prevalence of SSRI and SNRI use varied by country (1.8% in Norway to 7.0% in Iceland). Use and prescribed dosages decreased with each passing trimester of pregnancy; prevalence was 2.7% at conception, and 2.1%, 1.7% and 1.3% respectively in 1st, 2nd and 3rd trimester. In 0.6% of pregnancies women filled a prescription before pregnancy and in every trimester. In one third of exposed pregnancies, women were also dispensed anxiolytics, hypnotics or sedatives. Conclusion Use of SSRI and SNRI use during pregnancy varied between the Nordic countries, but the overall prevalence remained low and relatively stable from 2008 to 2012. The low prevalence of use and high proportion of women who discontinue treatment in pregnancy raise questions about adequate treatment of depression in pregnant women. PMID:26657647

  18. Childhood trauma predicts antidepressant response in adults with major depression: data from the randomized international study to predict optimized treatment for depression.

    PubMed

    Williams, L M; Debattista, C; Duchemin, A-M; Schatzberg, A F; Nemeroff, C B

    2016-05-03

    Few reliable predictors indicate which depressed individuals respond to antidepressants. Several studies suggest that a history of early-life trauma predicts poorer response to antidepressant therapy but results are variable and limited in adults. The major goal of the present study was to evaluate the role of early-life trauma in predicting acute response outcomes to antidepressants in a large sample of well-characterized patients with major depressive disorder (MDD). The international Study to Predict Optimized Treatment for Depression (iSPOT-D) is a randomized clinical trial with enrollment from December 2008 to January 2012 at eight academic and nine private clinical settings in five countries. Patients (n=1008) meeting DSM-IV criteria for MDD and 336 matched healthy controls comprised the study sample. Six participants withdrew due to serious adverse events. Randomization was to 8 weeks of treatment with escitalopram, sertraline or venlafaxine with dosage adjusted by the participant's treating clinician per routine clinical practice. Exposure to 18 types of traumatic events before the age of 18 was assessed using the Early-Life Stress Questionnaire. Impact of early-life stressors-overall trauma 'load' and specific type of abuse-on treatment outcomes measures: response: (⩾50% improvement on the 17-item Hamilton Rating Scale for Depression, HRSD17 or on the 16-item Quick Inventory of Depressive Symptomatology-Self-Rated, QIDS_SR16) and remission (score ⩽7 on the HRSD17 and ⩽5 on the QIDS_SR16). Trauma prevalence in MDD was compared with controls. Depressed participants were significantly more likely to report early-life stress than controls; 62.5% of MDD participants reported more than two traumatic events compared with 28.4% of controls. The higher rate of early-life trauma was most apparent for experiences of interpersonal violation (emotional, sexual and physical abuses). Abuse and notably abuse occurring at ⩽7 years of age predicted poorer outcomes

  19. Childhood trauma predicts antidepressant response in adults with major depression: data from the randomized international study to predict optimized treatment for depression

    PubMed Central

    Williams, L M; Debattista, C; Duchemin, A-M; Schatzberg, A F; Nemeroff, C B

    2016-01-01

    Few reliable predictors indicate which depressed individuals respond to antidepressants. Several studies suggest that a history of early-life trauma predicts poorer response to antidepressant therapy but results are variable and limited in adults. The major goal of the present study was to evaluate the role of early-life trauma in predicting acute response outcomes to antidepressants in a large sample of well-characterized patients with major depressive disorder (MDD). The international Study to Predict Optimized Treatment for Depression (iSPOT-D) is a randomized clinical trial with enrollment from December 2008 to January 2012 at eight academic and nine private clinical settings in five countries. Patients (n=1008) meeting DSM-IV criteria for MDD and 336 matched healthy controls comprised the study sample. Six participants withdrew due to serious adverse events. Randomization was to 8 weeks of treatment with escitalopram, sertraline or venlafaxine with dosage adjusted by the participant's treating clinician per routine clinical practice. Exposure to 18 types of traumatic events before the age of 18 was assessed using the Early-Life Stress Questionnaire. Impact of early-life stressors—overall trauma ‘load' and specific type of abuse—on treatment outcomes measures: response: (⩾50% improvement on the 17-item Hamilton Rating Scale for Depression, HRSD17 or on the 16-item Quick Inventory of Depressive Symptomatology—Self-Rated, QIDS_SR16) and remission (score ⩽7 on the HRSD17 and ⩽5 on the QIDS_SR16). Trauma prevalence in MDD was compared with controls. Depressed participants were significantly more likely to report early-life stress than controls; 62.5% of MDD participants reported more than two traumatic events compared with 28.4% of controls. The higher rate of early-life trauma was most apparent for experiences of interpersonal violation (emotional, sexual and physical abuses). Abuse and notably abuse occurring at ⩽7 years of age predicted poorer

  20. Peripheral proinflammatory markers associated with ketamine response in a preclinical model of antidepressant-resistance.

    PubMed

    Walker, Adam J; Foley, Brittany M; Sutor, Shari L; McGillivray, Jane A; Frye, Mark A; Tye, Susannah J

    2015-10-15

    Ketamine, N-methyl-d-aspartate (NMDA) receptor antagonist and anti-inflammatory agent, has rapid therapeutic effects in a subset of patients with more intractable forms of depression. Irregular proinflammatory cytokine and acute-reactive protein levels have been reported in clinical and preclinical depression research. We explored the association between the rapid antidepressant-like effects of ketamine and peripheral proinflammatory profile in a model of antidepressant-resistance. Male Wistar rats were pre-treated with ACTH-(1-24) 100μg/d or saline (0.9%) for 14d. Antidepressant-like effects were assessed with the forced swim test (FST). Ketamine (10mg/kg) significantly reduced immobility duration in saline-pretreated control animals. In contrast, a divergent response was observed in ACTH-pretreated antidepressant resistant animals, with 50% responders and 50% non-responders. Plasma samples were analyzed via enzyme-linked immunosorbent assay (ELISA) for interleukin 6 (IL-6), tumour necrosis factor alpha (TNFα) and C-reactive protein (CRP). Levels of CRP and TNFα differentiated ketamine responders and non-responders.

  1. Antidepressants and Driving in Older Adults: A Systematic Review.

    PubMed

    Cameron, Duncan H; Rapoport, Mark J

    2016-06-01

    With an increasing number of older drivers who are prescribed antidepressants, the potential consequences of antidepressant use on driving skills in an aging population are becoming a pressing issue. We conducted a systematic review using MEDLINE, targeting articles specifically pertaining to antidepressants and driving in a population or subgroup of older adults (≥ 55 years of age). The search yielded 267 references, nine of which pertained to the effects of antidepressants on driving in older adults. The single experimental study found imipramine to have detrimental effects on highway driving, whereas nefazodone did not. Seven of eight population-based studies reported a significant increased risk of involvement in a collision associated with antidepressant use. Although the studies indicated a negative effect of antidepressants on driving, the epidemiological designs cannot exclude the possibility that the underlying illness, generally major depression, is the culprit.

  2. Adsorption study of a commonly used antidepressant drug, fluoxetine hydrochloride, onto a crosslinked β-cyclodextrin-carboxymethylcellulose polymer.

    PubMed

    Bonenfant, Danielle; Mimeault, Murielle; Niquette, Patrick; Hausler, Robert

    2012-01-01

    A study was carried out by ultraviolet-visible (UV-vis) and Fourier transform infrared (FTIR) spectroscopies to establish the efficiency of adsorption of fluoxetine hydrochloride (FLU), onto a crosslinked β-cyclodextrin-carboxymethylcellulose (β-CD-CMC) polymer. The adsorption was performed in mixtures containing aqueous FLU solution at 20 mg/L and 0.01-0.30 g of the β-CD-CMC polymer, at 25 °C, and atmospheric pressure under stirring. The results have revealed that the adsorption is a rapid process and the polymer possesses a high affinity for FLU with an adsorption capacity of 5.076 mg of FLU/g of polymer. This adsorption may involve the formation of a stable inclusion compound β-CD-CMC/FLU through the penetration of the FLU aromatic ring (A and/or B) into the β-CD cavity, and a physical adsorption with the polymer network. The inclusion compound can be stabilized by the formation of H-bonds between the -CF(3) group of FLU and the 6'-OH group of β-CD, and van der Waals interactions between the FLU aromatic ring and β-CD cavity. The data from a kinetic study have also indicated that the adsorption process was well described by the pseudo-second-order kinetic model, in which the initial adsorption rate and constant were estimated at 1.938 mg/g min and 0.075 g/mg min, respectively. Moreover, the results of adsorption equilibrium fitted the Freundlich isotherm, indicating a multilayer coverage and heterogeneous surface. Together, these results suggest that the adsorption of FLU onto the crosslinked β-CD-CMC polymer could constitute an advantageous technology for removing this commonly used antidepressant drug from wastewater due to the high adsorption capacity of the polymer and non-toxic character of β-CD to humans and environment.

  3. Antidepressant augmentation with anti-inflammatory agents.

    PubMed

    Andrade, Chittaranjan

    2014-09-01

    Antidepressant augmentation strategies are commonly employed to treat depressed patients who do not respond to antidepressant monotherapy. Neuroinflammatory mechanisms have been implicated in depression, and nonsteroidal anti-inflammatory drugs (NSAIDs) have been found effective in animal models of depression both in monotherapy and when used to augment antidepressant drugs. However, results with NSAIDs have been mixed in human observational studies, with both better and worse depression outcomes reported. Four small (pooled N = 160) randomized controlled trials suggest that celecoxib (200-400 mg/d) augmentation of antidepressant medication improves 4-6 week outcomes in major depressive disorder. There are no data, however, to support the use of celecoxib or other NSAIDs in antidepressant-resistant depression. There are also concerns about adverse events associated with NSAID treatment, and about pharmacodynamic drug interactions between these drugs and serotonin reuptake inhibitors. A reasonable conclusion for the present is that NSAID augmentation of antidepressants is, at best, a tentative approach in nonrefractory major depression.

  4. Early antidepressant therapy for elderly patients.

    PubMed

    Freund, Karen M; Moskowitz, Mark A; Lin, Ting H; McKinlay, John B

    2003-01-01

    We studied factors affecting the management of depression in older patients, especially the use of early antidepressant therapy. We recruited 128 primary care physicians to view one version of a 5-minute videotape of an elderly patient with somatic symptoms that were suggestive of depression, and to complete an interview that assessed decision making. Using an experimental factorial design, 16 versions of the videotape were produced, holding constant the clinical features of the case, while varying the patient's age, race, sex, and socioeconomic status. Dependent variables were the physicians' probability assessment of depression and the recommendation of antidepressant medication after the first visit. Depression was considered a possible diagnosis by 121 physicians (95%) and the most likely diagnosis by 69 (54%). Sixteen physicians (13%) recommended antidepressant therapy after the first visit, and they were less likely than other physicians to order initial laboratory tests to assess the possibility of other conditions. Recommendations for antidepressant therapy was not associated with patient age, sex, race, or socioeconomic status, or with physician sex, race, or experience. Family physicians were more likely than internists to recommend an antidepressant (19% [12/64] vs. 6% [4/64], P = 0.04). Based on a 5-minute vignette, physicians were likely to recognize depression, independent of patient characteristics. Those recommending early antidepressant therapy were more likely to be in family medicine and less likely to investigate other diagnoses initially.

  5. A Comparison of Gene Expression Profiles between Glucocorticoid Responder and Non-Responder Bovine Trabecular Meshwork Cells Using RNA Sequencing

    PubMed Central

    Bermudez, Jaclyn Y.; Webber, Hannah C.; Brown, Bartley; Braun, Terry A.; Clark, Abbot F.; Mao, Weiming

    2017-01-01

    The most common ocular side effect of glucocorticoid (GC) therapy is GC-induced ocular hypertension (OHT) and GC-induced glaucoma (GIG). GC-induced OHT occurs in about 40% of the general population, while the other 60% are resistant. This study aims to determine the genes and pathways involved in differential GC responsiveness in the trabecular meshwork (TM). Using paired bovine eyes, one eye was perfusion-cultured with 100nM dexamethasone (DEX), while the fellow eye was used to establish a bovine TM (BTM) cell strain. Based on maximum IOP change in the perfused eye, the BTM cell strain was identified as a DEX-responder or non-responder strain. Three responder and three non-responder BTM cell strains were cultured, treated with 0.1% ethanol or 100nM DEX for 7 days. RNA and proteins were extracted for RNA sequencing (RNAseq), qPCR, and Western immunoblotting (WB), respectively. Data were analyzed using the human and bovine genome databases as well as Tophat2 software. Genes were grouped and compared using Student’s t-test. We found that DEX induced fibronectin expression in responder BTM cells but not in non-responder cells using WB. RNAseq showed between 93 and 606 differentially expressed genes in different expression groups between responder and non-responder BTM cells. The data generated by RNAseq were validated using qPCR. Pathway analyses showed 35 pathways associated with differentially expressed genes. These genes and pathways may play important roles in GC-induced OHT and will help us to better understand differential ocular responsiveness to GCs. PMID:28068412

  6. Antidepressant properties of the triazolobenzodiazepines alprazolam and adinazolam: studies on the olfactory bulbectomized rat model of depression.

    PubMed

    O'Connor, W T; Earley, B; Leonard, B E

    1985-01-01

    Chronically administered alprazolam and adinazolam attenuated the hyperactivity of bilaterally bulbectomized rats when placed in a stressful, novel environment ('open field' apparatus). These drugs had no effect on the activities of sham operated animals under the same experimental conditions. In other studies in these laboratories, clinically effective antidepressant drugs have been shown to have a qualitatively similar effect to alprazolam and adinazolam. Chronically administered diazepam and phenobarbitone did not affect the hyperactivity of bulbectomized rats in the 'open field' apparatus. No difference could be found between the behaviour of bulbectomized rats and the sham operated controls when the animals were placed in a novel, non-stressful environment ('hole board' apparatus and Y-maze). Chronic treatment of either the lesioned or non-lesioned animals with alprazolam or adinazolam did not cause any change in the behaviour of the animals in these situations. This suggests that the behaviour of the rat on the 'hole board' is not a reliable indication of anti-anxiety activity for chronically administered benzodiazepines. When unstarved lesioned and non-lesioned animals were given a choice of five palatable foods for a period of 1 h, slight differences in preference for the type of food chosen could be detected. Thus unsweetened biscuit ('cream crackers') was the most preferred choice of the sham operated rats while cheese and chocolate were the least preferred. Bulbectomized rats showed a more varied food choice, with processed meat ('corned beef') and raisins being preferred to biscuit in two out of four groups. Chronic treatment with either alprazolam or adinazolam did not appear to affect the food preference.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. CNS- and ANS-arousal predict response to antidepressant medication: Findings from the randomized iSPOT-D study.

    PubMed

    Olbrich, Sebastian; Tränkner, Anja; Surova, Galina; Gevirtz, Richard; Gordon, Evian; Hegerl, Ulrich; Arns, Martijn

    2016-02-01

    Arousal systems are one of the recently announced NIMH Research Domain Criteria to inform future diagnostics and treatment prediction. In major depressive disorder (MDD), altered central nervous system (CNS) wakefulness regulation and an increased sympathetic autonomic nervous system (ANS) activity have been identified as biomarkers with possible discriminative value for prediction of antidepressant treatment response. Therefore, the hypothesis of a more pronounced decline of CNS and ANS-arousal being predictive for a positive treatment outcome to selective-serotonin-reuptake-inhibitor (SSRI) treatment was derived from a small, independent exploratory dataset (N = 25) and replicated using data from the randomized international Study to Predict Optimized Treatment Response in Depression (iSPOT-D). There, 1008 MDD participants were randomized to either a SSRI (escitalopram or sertraline) or a serotonin-norepinephrine-reuptake-inhibitor (SNRI-venlafaxine) arm. Treatment response was established after eight weeks using the 17-item Hamilton Rating Scale for Depression. CNS-arousal (i.e. electroencephalogram-vigilance), ANS-arousal (heart rate) and their change across time were assessed during rest. Responders and remitters to SSRI treatment were characterized by a faster decline of CNS-arousal during rest whereas SNRI responders showed a significant increase of ANS-arousal. Furthermore, SSRI responders/remitters showed an association between ANS- and CNS-arousal regulation in comparison to non-responders/non-remitters while this was not the case for SNRI treatment arm. Since positive treatment outcome to SSRI and SNRI was linked to distinct CNS and ANS-arousal profiles, these predictive markers probably are not disorder specific alterations but reflect the responsiveness of the nervous system to specific drugs.

  8. Intravenous Lipid Emulsion Therapy Does Not Improve Hypotension Compared to Sodium Bicarbonate for Tricyclic Antidepressant Toxicity: A Randomized, Controlled Pilot Study in a Swine Model

    DTIC Science & Technology

    2014-11-01

    ORIGINAL CONTRIBUTION Intravenous Lipid Emulsion Therapy Does Not Improve Hypotension Compared to Sodium Bicarbonate for Tricyclic Antidepressant ...Maria Castaneda, MS Abstract Objectives: Tricyclic antidepressants (TCAs) are highly lipophilic medications used to treat posttraumatic stress disorder...Intravenous Lipid Emulsion Therapy Does Not Improve Hypotension Compared to Sodium Bicarbonate for Tricyclic Antidepressant Toxicity: A Randomized, Controlled

  9. Biological profiling of prospective antidepressant response in major depressive disorder: Associations with (neuro)inflammation, fatty acid metabolism, and amygdala-reactivity.

    PubMed

    Mocking, R J T; Nap, T S; Westerink, A M; Assies, J; Vaz, F M; Koeter, M W J; Ruhé, H G; Schene, A H

    2017-05-01

    A better understanding of factors underlying antidepressant non-response may improve the prediction of which patients will respond to what treatment. Major depressive disorder (MDD) is associated with alterations in fatty acid metabolism, (neuro)inflammation and amygdala-reactivity. However, their mutual relations, and the extent to which they are associated with prospective antidepressant-response, remain unknown. To test (I) alterations in (neuro)inflammation and its associations with fatty acid metabolism and amygdala-reactivity in MDD-patients compared to controls, and (II) whether these alterations are associated with prospective paroxetine response. We compared 70 unmedicated MDD-patients with 51 matched healthy controls at baseline, regarding erythrocyte membrane omega-6 arachidonic acid (AA), inflammation [serum (high-sensitivity) C-reactive protein (CRP)], and in a subgroup amygdala-reactivity to emotional faces using functional magnetic resonance imaging (fMRI) (N=42). Subsequently, we treated patients with 12 weeks paroxetine, and repeated baseline measures after 6 and 12 weeks to compare non-responders, early-responders (response at 6 weeks), and late-responders (response at 12 weeks). Compared to controls, MDD-patients showed higher CRP (p=0.016) and AA (p=0.019) after adjustment for confounders at baseline. AA and CRP were mutually correlated (p=0.043). In addition, patients showed a more negative relation between AA and left amygdala-reactivity (p=0.014). Moreover, AA and CRP were associated with antidepressant-response: early responders showed lower AA (p=0.018) and higher CRP-concentrations (p=0.008) than non-responders throughout the study. Higher observed CRP and AA, their mutual association, and relation with amygdala-reactivity, are corroborative with a role for (neuro)inflammation in MDD. In addition, observed associations of these factors with prospective antidepressant-response suggest a potential role as biomarkers. Future studies in

  10. Continued antidepressant treatment and suicide in patients with depressive disorder.

    PubMed

    Søndergård, Lars; Lopez, Ana Garcia; Andersen, Per Kragh; Kessing, Lars Vedel

    2007-01-01

    Antidepressant use in Denmark, as in many developed countries, has substantially increased during recent years, coinciding with a decreasing suicide rate. In a nationwide observational cohort study with linkage of registers of all prescribed antidepressants and recorded suicides in Denmark from 1995 to 2000, we investigated the relation between continued treatment with antidepressants and suicide in a population of all patients discharged from hospital psychiatry with a diagnosis of depressive disorder. Patients discharged from hospital psychiatry with a diagnosis of depressive disorder had a highly increased rate of suicide. Those who continued treatment with antidepressants had a decreased rate of suicide compared with those who purchased antidepressants once (rate ratio: 0.31, 95% confidence interval: 0.26-0.36). Further, the rate of suicide decreased consistently with the number of prescriptions. On individualized data from a cohort of patients with a known history of depressive disorder, continued antidepressant treatment was associated with reduced risk of suicide.

  11. Bleeding risk under selective serotonin reuptake inhibitor (SSRI) antidepressants: A meta-analysis of observational studies.

    PubMed

    Laporte, Silvy; Chapelle, Céline; Caillet, Pascal; Beyens, Marie-Noëlle; Bellet, Florelle; Delavenne, Xavier; Mismetti, Patrick; Bertoletti, Laurent

    2017-04-01

    Selective serotonin reuptake inhibitors (SSRIs) have been reported to be potentially associated with an increased risk of bleeding. A meta-analysis of observational studies was conducted to quantify this risk. Case-control and cohort studies investigating bleeding risk under SSRI therapy were retrieved by searching the Medline, Pascal, Google Scholar and Scopus databases. Case-control studies were included if they reported bleeding incidents with and without the use of SSRIs and cohort studies were included if they reported the rate of bleeds among SSRI users and non-users. The main outcome was severe bleeding, whatever the site. Only data concerning SSRI belonging to the ATC class N06AB were used. For both case-control and cohort studies, we recorded the adjusted effect estimates and their 95% confidence intervals (CI). Pooled adjusted odds ratio (OR) estimates were computed for case-control and cohort studies using an inverse-variance model. Meta-analysis of the adjusted ORs of 42 observational studies showed a significant association between SSRI use and the risk of bleeding [OR 1.41 (95% CI 1.27-1.57), random effect model, p<0.0001]. The association was found for the 31 case-control studies (1,255,073 patients), with an increased risk of 41% of bleeding [OR 1.41 (95% CI 1.25-1.60)], as well as for the 11 cohort studies including 187,956 patients [OR 1.36 (95% CI 1.12-1.64)]. Subgroup analyses showed that the association remained constant whatever the characteristics of studies. This meta-analysis shows an increased risk of bleeding of at least 36% (from 12% to 64%) based on the high-level of observational studies with SSRIs use.

  12. Tricyclic antidepressant use and risk of fractures: a meta-analysis of cohort and case-control studies.

    PubMed

    Wu, Qing; Qu, Wenchun; Crowell, Michael D; Hentz, Joseph G; Frey, Keith A

    2013-04-01

    Because studies of the association between tricyclic antidepressant (TCA) treatment and risk of fracture have shown inconsistent findings, we sought to assess whether people who take TCAs are at increased risk of fracture. Relevant studies published by June 2012 were identified through database searches of Scopus, MEDLINE, EMBASE, PsycINFO, ISI Web of Science, and WorldCat Dissertations and Theses from their inception, and manual searching of reference lists. Only original studies that examined the association between TCA treatment and risk of fracture were included. Two investigators independently conducted literature searches, study selection, study appraisal, and data abstraction using a standardized protocol. Disagreements were resolved by consensus. Twelve studies met inclusion criteria. Because of the heterogeneity of these studies, random-effects models were used to pool estimates of effect. Overall, TCA use was associated with significantly increased fracture risk (relative risk [RR], 1.45; 95% confidence interval [CI], 1.31-1.60; p < 0.001). Increased fracture risk associated with TCA use was also observed in studies that adjusted for bone mineral density (RR, 1.54; 95% CI, 1.24-1.90; p < 0.001) or depression (RR, 1.49; 95% CI, 1.28-1.67; p < 0.001). Strength of association with TCA exposure duration ≥6 weeks (RR, 1.13; 95% CI, 1.00-1.28) was substantially weaker than association with TCA exposure duration <6 weeks (RR, 2.40; 95% CI, 1.41-4.08). Prior TCA exposure had no significant effect on fracture risk (RR, 1.04; 95% CI, 0.86-1.26; p = 0.70). After accounting for publication bias, we found the overall association between TCA use and fracture risk to be slightly weaker (RR, 1.36; 95% CI, 1.24-1.50) but still significant (p < 0.001). Findings of this meta-analysis indicate that treatment with TCAs may convey an increased risk of fracture, independent of depression and bone mineral density.

  13. The effect of antidepressants on fertility.

    PubMed

    Casilla-Lennon, Marianne M; Meltzer-Brody, Samantha; Steiner, Anne Z

    2016-09-01

    Information on the effects of different pharmaceuticals on fertility is sparse. Human and animal models indicate that antidepressant use could have a negative effect on fertility through alteration of levels of the neurosteroid, allopregnanolone. The objective of this study is to assess the effects of antidepressants on the natural fertility in women. A secondary analysis of data from Time to Conceive, a prospective cohort study, was conducted. Women ages 30 to 44 years without a history of infertility, early in their attempts to conceive, were followed with standardized pregnancy testing until pregnancy was detected. Medication use was assessed at enrollment, daily for up to 4 months, and then monthly. For this analysis, discrete time regression models were created to calculate the association between antidepressant use and fecundability. Potential confounders-age, body mass index, caffeine, alcohol use, and education-were included in all models. Ninety-two (9.6%) of 957 women reported antidepressant use while attempting to conceive. Women taking antidepressants were more likely to be non-Hispanic Caucasian (91% vs 75%, P < .01) and to consume alcoholic beverages (74% vs 61%, P < .01). Antidepressant use at enrollment had an adjusted fecundability ratio (FR) of 0.86 (95% confidence interval [CI], 0.63-1.20). However, time-varying analyses suggested that antidepressant use in a given cycle is associated with a reduced probability of conceiving in that cycle (adjusted FR, 0.75; 95% CI, 0.53-1.06). After adjusting for history of depression or restricting the analysis to women who reported a history of depression, the association between antidepressant use and decreased fecundability remained [adjusted FR, 0.66 (95% CI, 0.45-0.97) and (adjusted FR, 0.64; 95% CI, 0.43-0.94), respectively]. Our data suggest that antidepressants may reduce the probability of a woman with a history of depression to conceive naturally. Future studies are needed to differentiate the extent

  14. Managing antidepression overdoses.

    PubMed

    Miller, Jim

    2004-10-01

    Depression is a physiological disorder that is medically treated by increasing the bodily amount of one or all of the following neurotransmitters: serotonin, dopamine and norepinephrine. Although there are seven distinct classes of antidepressants, prehospital care professionals should at minimum be able to distinguish the monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and newer antidepressants that are none of these. Monoamine oxidase inhibitors have severe, potentially life-threatening interactions with a variety of medications, including the paramedic drug meperidine, as well as with many common foods. An overdose of tricyclic antidepressants can cause lethal cardiac irregularities. Tricyclics are toxic to children in very small doses. A patient who has overdosed on TCAs may be walking and talking when you first arrive, then quickly deteriorate and die before your eyes. The treatment for TCA overdose is sodium bicarbonate; refer to your medical direction for dosages and indications. A common indication of TCA overdose, secondary to the patient's having access to the drugs, is widening of the QRS complex to greater than 0.12 seconds. Serotonin syndrome is often the result of taking a new generation antidepressant, such as an SSRI, while there is still TCA or MAOI in the bloodstream.

  15. A comparison of small monetary incentives to convert survey non-respondents: a randomized control trial

    PubMed Central

    2011-01-01

    Background Maximizing response rates is critically important in order to provide the most generalizable and unbiased research results. High response rates reduce the chance of respondents being systematically different from non-respondents, and thus, reduce the risk of results not truly reflecting the study population. Monetary incentives are often used to improve response rates, but little is known about whether larger incentives improve response rates in those who previously have been unenthusiastic about participating in research. In this study we compared the response rates and cost-effectiveness of a $5 versus $2 monetary incentive accompanying a short survey mailed to patients who did not respond or refused to participate in research study with a face-to-face survey. Methods 1,328 non-responders were randomly assigned to receive $5 or $2 and a short, 10-question survey by mail. Reminder postcards were sent to everyone; those not returning the survey were sent a second survey without incentive. Overall response rates, response rates by incentive condition, and odds of responding to the larger incentive were calculated. Total costs (materials, postage, and labor) and incremental cost-effectiveness ratios were also calculated and compared by incentive condition. Results After the first mailing, the response rate within the $5 group was significantly higher (57.8% vs. 47.7%, p < .001); after the second mailing, the difference narrowed by 80%, resulting in a non-significant difference in cumulative rates between the $5 and $2 groups (67.3% vs. 65.4%, respectively, p = .47). Regardless of incentive or number of contacts, respondents were significantly more likely to be male, white, married, and 50-75 years old. Total costs were higher with the larger versus smaller incentive ($13.77 versus $9.95 per completed survey). Conclusions A $5 incentive provides a significantly higher response rate than a $2 incentive if only one survey mailing is used but not if two survey

  16. Results and their implications from comparing respondents and proxy responses for non-respondents with cognitive difficulties on a telephone survey.

    PubMed

    Adams, Mary

    2017-01-01

    Limited study has been done on proxy responses for non-respondents with subjective cognitive decline (SCD) on the Behavioral Risk Factor Surveillance System (BRFSS). To directly compare results for survey respondents with SCD with those for proxies provided for non-respondents with SCD. Publicly available 2011 BRFSS data from 120,485 households in 21 states were analyzed using Stata. Respondents ages 40 and older with SCD (n = 10,831) were compared with proxy responses for non-respondents ages 40 and older with SCD (n = 4296) living in households where the respondent did not have SCD. Outcome measures included functional difficulties associated with their SCD, needing help, receiving informal care, talking with a healthcare provider about their SCD, getting treatment, and having a dementia diagnosis. Logistic regression for each outcome controlled for age, household income, state of residence, and number of household adults. Non-respondents were significantly more likely than respondents by Pearson chi square tests with alpha = 0.05 to report all 6 outcomes. Adjusted odds ratios comparing non-respondents with respondents ranged from 2.61 (95% confidence interval: 2.22-3.07) for needing help, to 8.99 (6.60-12.24) for a dementia diagnosis and confirmed unadjusted results. Respondent results only represent adults capable of answering a telephone survey. To represent all household adults and avoid nonresponse bias that may under-represent the true population parameters by as much as 70%, results must include both respondents and non-respondents. Other measures may be similarly affected if they inhibit one's ability to respond to a telephone survey (e.g. disability, stroke). Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Sleep homeostatic pressure and PER3 VNTR gene polymorphism influence antidepressant response to sleep deprivation in bipolar depression.

    PubMed

    Dallaspezia, Sara; Locatelli, Clara; Lorenzi, Cristina; Pirovano, Adele; Colombo, Cristina; Benedetti, Francesco

    2016-03-01

    Combined Total sleep deprivation (TSD) and light therapy (LT) cause a rapid improvement in bipolar depression which has been hypothesized to be paralleled by changes in sleep homeostasis. Recent studies showed that bipolar patients had lower changes of EEG theta power after sleep and responders to antidepressant TSD+LT slept less and showed a lower increase of EEG theta power then non-responders. A polymorphism in PER3 gene has been associated with diurnal preference, sleep structure and homeostatic response to sleep deprivation in healthy subjects. We hypothesized that the individual variability in the homeostatic response to TSD could be a correlate of antidepressant response and be influenced by genetic factors. We administered three TSD+LT cycles to bipolar depressed patients. Severity of depression was rated on Hamilton Depression Rating Scale. Actigraphic recordings were performed in a group of patients. PER3 polymorphism influenced changes in total sleep time (F=2.24; p=0.024): while PER3(4/4) and PER3(4/5) patients showed a reduction in it after treatment, PER3(5/5) subjects showed an increase of about 40min, suggesting a higher homeostatic pressure. The same polymorphism influenced the change of depressive symptomatology during treatment (F=3.72; p=0.028). Sleep information was recorded till the day after the end of treatment: a longer period of observation could give more information about the possible maintenance of allostatic adaptation. A higher sleep homeostatic pressure reduced the antidepressant response to TSD+LT, while an allostatic adaptation to sleep loss was associated with better response. This process seems to be under genetic control. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Mortality and Cumulative Exposure to Antipsychotics, Antidepressants, and Benzodiazepines in Patients With Schizophrenia: An Observational Follow-Up Study.

    PubMed

    Tiihonen, Jari; Mittendorfer-Rutz, Ellenor; Torniainen, Minna; Alexanderson, Kristina; Tanskanen, Antti

    2016-06-01

    Although mortality related to psychotropic medications has received much attention in recent years, little is known about the relationship between risk of death and cumulative antipsychotic load, and even less about the relationship between mortality and cumulative exposure to antidepressants or benzodiazepines. The authors examined these relationships using nationwide databases. The authors used prospectively collected nationwide databases to identify all individuals 16-65 years of age with a schizophrenia diagnosis (N=21,492) in Sweden. All-cause and cause-specific mortality rates were calculated as a function of cumulative low, moderate, and high exposure to antipsychotics, antidepressants, and benzodiazepines from 2006 through 2010. Compared with no exposure, both moderate (adjusted hazard ratio=0.59, 95% CI=0.49-0.70) and high (adjusted hazard ratio=0.75, 95% CI=0.63-0.89) antipsychotic exposures were associated with substantially lower overall mortality. Moderate antidepressant exposure was associated with a lower mortality (adjusted hazard ratio=0.85, 95% CI=0.73-0.98), and high exposure, even lower (adjusted hazard ratio=0.71, 95% CI=0.59-0.86). Exposure to benzodiazepines showed a dose-response relationship with mortality (hazard ratios up to 1.74 [95% CI=1.50-2.03]). Moderate and high-dose antipsychotic and antidepressant use were associated with 15%-40% lower overall mortality, whereas chronic high-dose use of benzodiazepines was associated with up to a 70% higher risk of death compared with no exposure. Since patients with anxiety and depressive symptoms may have a higher intrinsic risk of death, the finding for benzodiazepines may be attributable to some extent to residual confounding.

  19. Polypharmacy with antidepressants in children and adolescents.

    PubMed

    Díaz-Caneja, Covadonga M; Espliego, Ana; Parellada, Mara; Arango, Celso; Moreno, Carmen

    2014-07-01

    The aim of this study was to review current epidemiological data on the use of antidepressants in co-prescription with other psychotropic drugs in children and adolescents, as well as available efficacy and safety information. A Medline search from inception until February 2012 was performed to identify epidemiological and clinical studies, reviews and reports containing potentially relevant information on polypharmacy with antidepressants in young people. There has been an increase in polypharmacy in children and adolescents involving antidepressants in recent years. Antidepressants have become one of the drug classes most frequently prescribed in combination and are commonly co-prescribed with stimulants and antipsychotics. Most information regarding efficacy and safety of polypharmacy patterns was provided by case series and open-label studies. Efficacy studies gave some support for the use of a combination of antidepressants and antipsychotics in the management of refractory obsessive-compulsive disorder and some residual symptoms in major depressive disorder. Even less empirical support was found for a combination of stimulants and antidepressants in co-morbid attention deficit hyperactivity disorder and mood or anxiety disorders. Adverse events were similar to those found with individual medication groups, with severe adverse events mostly reported by individual case reports. The use of polypharmacy with antidepressants has become a regular practice in clinical settings. Although there is still little efficacy and safety information, preliminary evidence points to the potential clinical usefulness of some polypharmacy patterns. Further research on patients with co-morbidities or more severe conditions is needed, in order to improve knowledge of this issue.

  20. Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports

    PubMed Central

    Guski, Louise Schow; Freund, Nanna; Gøtzsche, Peter C

    2016-01-01

    Objective To study serious harms associated with selective serotonin and serotonin-norepinephrine reuptake inhibitors. Design Systematic review and meta-analysis. Main outcome measures Mortality and suicidality. Secondary outcomes were aggressive behaviour and akathisia. Data sources Clinical study reports for duloxetine, fluoxetine, paroxetine, sertraline, and venlafaxine obtained from the European and UK drug regulators, and summary trial reports for duloxetine and fluoxetine from Eli Lilly’s website. Eligibility criteria for study selection Double blind placebo controlled trials that contained any patient narratives or individual patient listings of harms. Data extraction and analysis Two researchers extracted data independently; the outcomes were meta-analysed by Peto’s exact method (fixed effect model). Results We included 70 trials (64 381 pages of clinical study reports) with 18 526 patients. These trials had limitations in the study design and discrepancies in reporting, which may have led to serious under-reporting of harms. For example, some outcomes appeared only in individual patient listings in appendices, which we had for only 32 trials, and we did not have case report forms for any of the trials. Differences in mortality (all deaths were in adults, odds ratio 1.28, 95% confidence interval 0.40 to 4.06), suicidality (1.21, 0.84 to 1.74), and akathisia (2.04, 0.93 to 4.48) were not significant, whereas patients taking antidepressants displayed more aggressive behaviour (1.93, 1.26 to 2.95). For adults, the odds ratios were 0.81 (0.51 to 1.28) for suicidality, 1.09 (0.55 to 2.14) for aggression, and 2.00 (0.79 to 5.04) for akathisia. The corresponding values for children and adolescents were 2.39 (1.31 to 4.33), 2.79 (1.62 to 4.81), and 2.15 (0.48 to 9.65). In the summary trial reports on Eli Lilly’s website, almost all deaths were noted, but all suicidal ideation events were missing, and the information on the remaining outcomes was

  1. Rapid-acting glutamatergic antidepressants: the path to ketamine and beyond

    PubMed Central

    Krystal, John H.; Sanacora, Gerard; Duman, Ronald S.

    2013-01-01

    Traditional antidepressants require many weeks to reveal their therapeutic effects. However, the widely replicated observation that a single subanesthetic dose of the NMDA glutamate receptor antagonist, ketamine, produced meaningful clinical improvement within hours suggested that rapidly acting antidepressants might be possible. The ketamine studies stimulated a new generation of basic antidepressant research that identified new neural signaling mechanisms in antidepressant response and provided a conceptual framework linking a group of novel antidepressant mechanisms. This article presents the path that led to the testing of ketamine, considers its promise as an antidepressant, and reviews novel treatment mechanisms that are emerging from this line of research. PMID:23726151

  2. [Poisoning with antidepressants].

    PubMed

    Bodmer, Michael

    2009-05-01

    Intoxications with medications are among the most frequent diagnoses in patients admitted to medical emergency departments and intensive care units. Due to their particular toxicity tricyclic antidepressants play an important role despite a decreasing incidence. Tricyclic antidepressant toxicity includes an inhibition of myocardial excitability, central (sedation, seizures) and peripheral anticholinergic signs, and arterial hypotension. Cardiac arrhythmia including ventricular tachycardia and fibrillation, sustained seizures and severe central anticholinergic symptoms such as agitation, delirium, and hyperthermia, are life threatening. Important treatment options include gastrointestinal decontamination with oral single-dose activated charcoal within 1-2 hours post ingestion, and antidotal therapy with boluses of sodium bicarbonate for cardiotoxicity. The selective serotonin reuptake inhibitors (SSRI) and the atypical antidepressants are far less toxic than tricyclics. They may lead to serotonin toxicity (serotonin syndrome).

  3. Comparative Efficacy of Newer Antidepressants in Combination with Pregabalin for Fibromyalgia Syndrome: A Controlled, Randomized Study.

    PubMed

    Ramzy, Eiad A

    2017-01-01

    This controlled, randomized study investigated the hypothesis that the combined use of pregabalin plus paroxetine for fibromyalgia management would be associated with comparable Somatic Symptoms Scale-8 (SSS-8) and Center for Epidemiological Studies Depression Scale (CESDS) scores, but higher tolerability than the combined use of pregabalin plus either amitriptyline or venlafaxine. After institutional ethics committee approval, 75 female subjects diagnosed with fibromyalgia and in receipt of pregabalin (75 mg/day) were randomly allocated to concurrently receive amitriptyline (25 mg/day; n = 24), venlafaxine (75 mg/day; n = 25), or paroxetine (25 mg/day; n = 26). All patients were assessed bimonthly for 6 consecutive months for changes in SSS-8 and CESDS scores, life satisfaction, mood, sleep quality, fatigue, medication tolerability, and adverse events. Compared with pregabalin plus amitriptyline or venlafaxine, the combined use of pregabalin plus paroxetine in fibromyalgia patients resulted in significantly lower SSS-8 and CESDS scores from 18 (P < 0.05) and 10 weeks (P < 0.001) after the initiation of study medications, respectively; higher medication tolerability (P < 0.001); improved life satisfaction, mood, and sleep quality at most observation times (P < 0.05); and fewer instances of dry mouth and elevated blood pressure (P < 0.02). Medication termination due to poor tolerability was observed most frequently in the venlafaxine group (P < 0.05), while drowsiness, dizziness, blurred vision, abnormal taste, hunger, hallucination, urination problems, and sexual dysfunction were observed most frequently in the amitriptyline group (P < 0.02). The combined use of pregabalin plus paroxetine offers an effective method with increased tolerability to reduce the somatic and depressive symptoms of fibromyalgia and to enhance the quality of life in affected individuals. © 2016 World Institute of Pain.

  4. Low dose revaccination induces robust protective anti-HBs antibody response in the majority of healthy non-responder neonates.

    PubMed

    Jafarzadeh, A; Zarei, S; Shokri, F

    2008-01-10

    A sizeable proportion (1-10%) of healthy adults and to lesser extent neonates vaccinated with triple 10 microg hepatitis B (HB) vaccine fail to mount a protective antibody response. Revaccination with the same vaccine dose has proved to be effective in a significant number of primary non-responders. The influence of revaccination with lower vaccine doses however has not been studied adequately in non-responder neonates. This study was conducted to evaluate the influence of supplementary vaccination with a single low and standard dose of a recombinant hepatitis B (HB) vaccine in healthy Iranian non-responder neonates to primary vaccination. Iranian neonates unable to respond to primary vaccination with 10, 5 or 2.5 microg doses of recombinant HB vaccine were revaccinated with a single additional dose of the same concentration. Serum anti-HBs antibody titer was measured by sandwich ELISA. Administration of a single additional dose induced seroprotection (anti-HBs> or =10IU/L) in 10/12 (83%), 10/12 (83%) and 21/24 (87.5%) of non-responder neonates in 10, 5 and 2.5 microg vaccine recipients with geometric mean titers (and 95% confidence limits) of 1358 (258-7142), 401 (79-2038) and 164 (62-433) IU/L, respectively. The log-transformed antibody titer obtained for the 10 microg dose recipients was significantly higher than that of the 2.5 microg dose vaccinees (p=0.028). No significant differences in anti-HBs titer were observed between other groups of vaccinees. However, the total seroprotection rates obtained after administration of four low doses of 2.5 and 5 microg were significantly higher than that obtained after administration of the classical three 10 microg doses (p=0.029 and p=0.006, respectively). The total seroprotection rates were similar between all groups of vaccines receiving four doses of 2.5, 5 and 10 microg vaccine doses. These results indicate that a significant proportion of non-responder neonates can be induced to develop a protective anti

  5. Mechanisms of antidepressant resistance

    PubMed Central

    El-Hage, Wissam; Leman, Samuel; Camus, Vincent; Belzung, Catherine

    2013-01-01

    Depression is one of the most frequent and severe mental disorder. Since the discovery of antidepressant (AD) properties of the imipramine and then after of other tricyclic compounds, several classes of psychotropic drugs have shown be effective in treating major depressive disorder (MDD). However, there is a wide range of variability in response to ADs that might lead to non response or partial response or in increased rate of relapse or recurrence. The mechanisms of response to AD therapy are poorly understood, and few biomarkers are available than can predict response to pharmacotherapy. Here, we will first review markers that can be used to predict response to pharmacotherapy, such as markers of drug metabolism or blood-brain barrier (BBB) function, the activity of specific brain areas or neurotransmitter systems, hormonal dysregulations or plasticity, and related molecular targets. We will describe both clinical and preclinical studies and describe factors that might affect the expression of these markers, including environmental or genetic factors and comorbidities. This information will permit us to suggest practical recommendations and innovative treatment strategies to improve therapeutic outcomes. PMID:24319431

  6. Early identification of non-responding locally advanced breast tumors receiving neoadjuvant chemotherapy

    NASA Astrophysics Data System (ADS)

    Van de Giessen, Martijn; Schaafsma, Boudewijn E.; Charehbili, Ayoub; Smit, Vincent T. H. B. M.; Kroep, Judith R.; Lelieveldt, Boudewijn P. F.; Liefers, Gerrit-Jan; Chan, Alan; Löwik, Clemens W. G. M.; Dijkstra, Jouke; van de Velde, Cornelis J. H.; Wasser, Martin N. J. M.; Vahrmeijer, Alexander L.

    2015-02-01

    Diffuse optical spectroscopy (DOS) may be advantageous for monitoring tumor response during chemotherapy treatment, particularly in the early treatment stages. In this paper we perform a second analysis on the data of a clinical trial with 25 breast cancer patients that received neoadjuvant chemotherapy. Patients were monitored using delayed contrast enhanced MRI and additionally with diffuse optical spectroscopy at baseline, after 1 cycle of chemotherapy, halfway therapy and before surgery. In this analysis hemoglobin content between tumor tissue and healthy tissue of the same breast is compared on all four monitoring time points. Furthermore, the predictive power of the tumor-healthy tissue difference of HbO2 for non-responder prediction is assessed. The difference in HbO2 content between tumor and healthy tissue was statistically significantly higher in responding tumors than in non-responding tumors at baseline (10.88 vs -0.57 μM, P=0.014) and after one cycle of chemotherapy (6.45 vs -1.31 μM, P=0.048). Before surgery this difference had diminished. In the data of this study, classification on the HbO2 difference between tumor and healthy tissue was able to predict tumor (non-)response at baseline and after 1 cycle with an area-under-curve of 0.95 and 0.88, respectively. While this result suggests that tumor response can be predicted before chemotherapy onset, one should be very careful with interpreting these results. A larger patient population is needed to confirm this finding.

  7. Suicides and Suicide Attempts during Long-Term Treatment with Antidepressants: A Meta-Analysis of 29 Placebo-Controlled Studies Including 6,934 Patients with Major Depressive Disorder.

    PubMed

    Braun, Cora; Bschor, Tom; Franklin, Jeremy; Baethge, Christopher

    It is unclear whether antidepressants can prevent suicides or suicide attempts, particularly during long-term use. We carried out a comprehensive review of long-term studies of antidepressants (relapse prevention). Sources were obtained from 5 review articles and by searches of MEDLINE, PubMed Central and a hand search of bibliographies. We meta-analyzed placebo-controlled antidepressant RCTs of at least 3 months' duration and calculated suicide and suicide attempt incidence rates, incidence rate ratios and Peto odds ratios (ORs). Out of 807 studies screened 29 were included, covering 6,934 patients (5,529 patient-years). In total, 1.45 suicides and 2.76 suicide attempts per 1,000 patient-years were reported. Seven out of 8 suicides and 13 out of 14 suicide attempts occurred in antidepressant arms, resulting in incidence rate ratios of 5.03 (0.78-114.1; p = 0.102) for suicides and of 9.02 (1.58-193.6; p = 0.007) for suicide attempts. Peto ORs were 2.6 (0.6-11.2; nonsignificant) and 3.4 (1.1-11.0; p = 0.04), respectively. Dropouts due to unknown reasons were similar in the antidepressant and placebo arms (9.6 vs. 9.9%). The majority of suicides and suicide attempts originated from 1 study, accounting for a fifth of all patient-years in this meta-analysis. Leaving out this study resulted in a nonsignificant incidence rate ratio for suicide attempts of 3.83 (0.53-91.01). Therapists should be aware of the lack of proof from RCTs that antidepressants prevent suicides and suicide attempts. We cannot conclude with certainty whether antidepressants increase the risk for suicide or suicide attempts. Researchers must report all suicides and suicide attempts in RCTs. © 2016 S. Karger AG, Basel.

  8. Histamine H₁ receptor occupancy by the new-generation antidepressants fluvoxamine and mirtazapine: a positron emission tomography study in healthy volunteers.

    PubMed

    Sato, Hirotoshi; Ito, Chihiro; Tashiro, Manabu; Hiraoka, Kotaro; Shibuya, Katsuhiko; Funaki, Yoshihito; Iwata, Ren; Matsuoka, Hiroo; Yanai, Kazuhiko

    2013-11-01

    Histamine H₁ antagonists have hypnotic, appetite-promoting, and sedative effects. The affinities of various antidepressants for histamine receptors have only been partially determined in vitro and animal study. Positron emission tomography (PET) can clarify the in vivo dynamics of antidepressants at histamine receptors. We performed human PET imaging with [¹¹C]doxepin, a selective PET ligand of the histamine H₁ receptor (H₁R), to study the in vivo affinities of fluvoxamine and mirtazapine for the H₁R. The subjects were five male healthy Japanese volunteers. We performed cross-randomized PET imaging after single oral administration of fluvoxamine (25mg), mirtazapine (15 mg), or placebo. PET data were analyzed by region-of-interest and voxel-by-voxel analysis. We concurrently measured plasma drug concentrations, using liquid chromatography/tandem mass spectrometry and subjective sleepiness. The binding potential ratio of mirtazapine in brain cortex was significantly lower than that of fluvoxamine or placebo. Fluvoxamine did not occupy the H₁R, whereas H₁R occupancy (H₁RO) of mirtazapine reached 80-90 % in the cerebral neocortex. In the voxel-by-voxel analysis, the binding potential of mirtazapine was significantly lower than placebo in the dorsolateral prefrontal cortex, lateral temporal cortex, anterior cingulate gyrus, and posterior cingulate gyrus. The H₁RO of mirtazapine depended on the plasma drug concentration (AUC(0-180 min)) and was related to subjective sleepiness. Our results demonstrate a low affinity of fluvoxamine and a very high affinity of mirtazapine for the human brain H₁R in vivo. This study provides a basis for investigating the efficacy of new-generation antidepressants in central histamine systems.

  9. Referral for psychological therapy of people with long term conditions improves adherence to antidepressants and reduces emergency department attendance: Controlled before and after study

    PubMed Central

    de Lusignan, Simon; Chan, Tom; Tejerina Arreal, Maria C.; Parry, Glenys; Dent-Brown, Kim; Kendrick, Tony

    2013-01-01

    Background Referral to psychological therapies is recommended for people with common mental health problems (CMHP) however its impact on healthcare utilisation in people with long term conditions (LTCs) is not known. Method Routinely collected primary care, psychological therapy clinic and hospital data were extracted for the registered population of 20 practices (N = 121199). These data were linked using the SAPREL (Secure and Private Record Linkage) method. We linked the 1118 people referred to psychological therapies with 6711 controls, matched for age, gender and practice. We compared utilisation of healthcare resources by people with LTCs, 6 months before and after referral, and conducted a controlled before and after study to compare health utilisation with controls. We made the assumption that collection of a greater number of repeat prescriptions for antidepressants was associated with greater adherence. Results Overall 21.8% of people with an LTC had CMHP vs. 18.8% without (p < 0.001). People with LTCs before referral were more likely to use health care resources (2-tailed t-test p < 0.001). Cases with LTCs showed referral to the psychological therapies clinic was associated with increased antidepressant medication prescribing (mean differences 0.62, p < 0.001) and less use of emergency department than controls (mean difference −0.21, p = 0.003). Conclusions Referral to improved access to psychological therapies (IAPT) services appears of value to people with LTC. It is associated with the issue of a greater number of prescriptions for anti-depressant medicines and less use of emergency services. Further studies are needed to explore bed occupancy and outpatient attendance. PMID:23639304

  10. A Breathing-Based Meditation Intervention for Patients With Major Depressive Disorder Following Inadequate Response to Antidepressants: A Randomized Pilot Study.

    PubMed

    Sharma, Anup; Barrett, Marna S; Cucchiara, Andrew J; Gooneratne, Nalaka S; Thase, Michael E

    2017-01-01

    To evaluate feasibility, efficacy, and tolerability of Sudarshan Kriya yoga (SKY) as an adjunctive intervention in patients with major depressive disorder (MDD) with inadequate response to antidepressant treatment. Patients with MDD (defined by DSM-IV-TR) who were depressed despite ≥ 8 weeks of antidepressant treatment were randomized to SKY or a waitlist control (delayed yoga) arm for 8 weeks. The primary efficacy end point was change in 17-item Hamilton Depression Rating Scale (HDRS-17) total score from baseline to 2 months. The key secondary efficacy end points were change in Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) total scores. Analyses of the intent-to-treat (ITT) and completer sample were performed. The study was conducted at the University of Pennsylvania between October 2014 and December 2015. In the ITT sample (n = 25), the SKY arm (n = 13) showed a greater improvement in HDRS-17 total score compared to waitlist control (n = 12) (-9.77 vs 0.50, P = .0032). SKY also showed greater reduction in BDI total score versus waitlist control (-17.23 vs -1.75, P = .0101). Mean changes in BAI total score from baseline were significantly greater for SKY than waitlist (ITT mean difference: -5.19; 95% CI, -0.93 to -9.34; P = .0097; completer mean difference: -6.23; 95% CI, -1.39 to -11.07; P = .0005). No adverse events were reported. Results of this randomized, waitlist-controlled pilot study suggest the feasibility and promise of an adjunctive SKY-based intervention for patients with MDD who have not responded to antidepressants. ClinicalTrials.gov identifier: NCT02616549.

  11. A Breathing-based Meditation Intervention for Patients with Major Depressive Disorder Following Inadequate Response to Antidepressants: A Randomized Pilot Study

    PubMed Central

    Sharma, Anup; Barrett, Marna S.; Cucchiara, Andrew J.; Gooneratne, Nalaka S.; Thase, Michael E.

    2016-01-01

    Objective To evaluate feasibility, efficacy and tolerability of Sudarshan Kriya yoga (SKY) as an adjunctive intervention in patients with major depressive disorder (MDD) with inadequate response to antidepressant treatment. Method Patients with MDD (defined by DSM-IV-TR) depressed despite ≥8 weeks of antidepressant treatment were randomized to SKY or a waitlist control (delayed yoga) arm for 8 weeks. The primary efficacy end point was change in 17-item Hamilton Depression Rating Scale (HDRS-17) total score from baseline to 2 months. The key secondary efficacy end points were change in Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) total scores. Analyses of the intent-to-treat (ITT) and completer sample were performed. The study was conducted at the University of Pennsylvania between October 2014 and December 2015. Results In the ITT sample (n=25), the SKY arm (n=13) showed a greater improvement in HDRS-17 total score compared to waitlist control (n=12)(−9.77 vs. 0.50, P =.0032). SKY also showed greater reduction in BDI total score versus waitlist control (−17.23 vs. −1.75, P = .0101). Mean changes in Beck Anxiety Inventory (BAI) total score from baseline were significantly greater for SKY than waitlist (ITT mean difference: −5.19; 95% CI −0.93 to −9.34; P = .0097; completer mean difference: −6.23; 95% CI −1.39 to −11.07; P = .0005). No adverse events were reported. Conclusion Results of this randomized, waitlist-controlled pilot study suggest the feasibility and promise of an adjunctive SKY-based intervention for patients with MDD who have not responded to antidepressants. Trial Registration ClinicalTrials.gov identifier: NCT02616549 PMID:27898207

  12. On the nature of non-responding in discrimination learning with and without errors1

    PubMed Central

    Terrace, H. S.

    1974-01-01

    In human subjects, discrimination learning with errors results in active responding incompatible with the reinforced response. The direction of such incompatible behavior is opposite to that of the reinforced response. Responding occurs only during the stimulus correlated with extinction. The frequency of active non-responding is maximal shortly after the start of discrimination training (the time at which the frequency of errors decreases most rapidly) and approaches zero as discrimination training continues. The magnitude of behavioral contrast is not related systematically to the number of errors. Instead it is related directly to the frequency of active non-responding. Active non-responding appears to be motivated by the aversiveness of self-produced frustration, in the sense that active non-responding allows the subject to avoid the aversiveness of non-reinforced responding. ImagesFig. 1.Fig. 2. PMID:16811774

  13. Pretreatment cognitive and neural differences between sapropterin dihydrochloride responders and non-responders with phenylketonuria.

    PubMed

    Hawks, Zoë; Shimony, Joshua; Rutlin, Jerrel; Grange, Dorothy K; Christ, Shawn E; White, Desirée A

    2017-09-01

    Sapropterin dihydrochloride (BH4) reduces phenylalanine (Phe) levels and improves white matter integrity in a subset of individuals with phenylketonuria (PKU) known as "responders." Although prior research has identified biochemical and genotypic differences between BH4 responders and non-responders, cognitive and neural differences remain largely unexplored. To this end, we compared intelligence and white matter integrity prior to treatment with BH4 in 13 subsequent BH4 responders with PKU, 16 subsequent BH4 non-responders with PKU, and 12 healthy controls. Results indicated poorer intelligence and white matter integrity in non-responders compared to responders prior to treatment. In addition, poorer white matter integrity was associated with greater variability in Phe across the lifetime in non-responders but not in responders. These results underscore the importance of considering PKU as a multi-faceted, multi-dimensional disorder and point to the need for additional research to delineate characteristics that predict response to treatment with BH4.

  14. Heart rate variability in major depressive disorder and after antidepressant treatment with agomelatine and paroxetine: Findings from the Taiwan Study of Depression and Anxiety (TAISDA).

    PubMed

    Yeh, Ta-Chuan; Kao, Lien-Cheng; Tzeng, Nian-Sheng; Kuo, Terry B J; Huang, San-Yuan; Chang, Chuan-Chia; Chang, Hsin-An

    2016-01-04

    Evidence from previous studies suggests that heart rate variability (HRV) is reduced in major depressive disorder (MDD). However, whether this reduction is attributable to the disorder per se or to medication, since antidepressants may also affect HRV, is still debated. There is a dearth of information regarding the effects of agomelatine, a novel antidepressant, on HRV. Here, we investigated whether HRV is reduced in MDD and compared the effects of agomelatine and paroxetine on HRV. We recruited 618 physically healthy unmedicated patients with MDD and 506 healthy volunteers aged 20-65 years. Frequency-domain measures of resting HRV were obtained at the time of enrollment for all participants. For patients with MDD, these measures were obtained again after 6 weeks of either agomelatine or paroxetine monotherapy. Compared with healthy subjects, unmedicated patients with MDD exhibited significantly lower variance (total HRV), low frequency (LF), and high frequency (HF) HRV, and a higher LF/HF ratio. Depression severity independently contributed to decreased HRV and vagal tone. Fifty-six patients completed the open-label trial (n=29 for agomelatine, n=27 for paroxetine). Between-group analyses showed a significant group-by-time interaction for LF-HRV and HF-HRV, driven by increases in LF-HRV and HF-HRV only after agomelatine treatment. Within the paroxetine-treated group, there were no significant changes in mean R-R intervals or any HRV indices. We therefore concluded that MDD is associated with reduced HRV, which is inversely related to depression severity. Compared with paroxetine, agomelatine has a more vagotonic effect, suggesting greater cardiovascular safety. Clinicians should consider HRV effects while selecting antidepressants especially for depressed patients who already have decreased cardiac vagal tone. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Differences in reporting serious adverse events in industry sponsored clinical trial registries and journal articles on antidepressant and antipsychotic drugs: a cross-sectional study

    PubMed Central

    Hughes, Shannon; Cohen, David; Jaggi, Rachel

    2014-01-01

    Objective To examine the degree of concordance in reporting serious adverse events (SAEs) from antidepressant and antipsychotic drug trials among journal articles and clinical trial summaries, and to categorise types of discrepancies. Design Cross-sectional study of summaries of all antidepressant and antipsychotic trials included in an online trial registry and their first associated stand-alone journal articles. Setting Clinicalstudyresults.org, sponsored by Pharmaceutical Research and Manufacturers of America; clinicaltrials.gov, administered by the US National Institutes of Health. Main outcome measure 3 coders extracted data on the numbers and types of SAEs. Results 244 trial summaries for six antidepressant and antipsychotic drugs were retrieved, 142 (58.2%) listing an associated article. Of 1608 SAEs in drug-treated participants according to trial summaries, 694 (43.2%) did not appear in associated articles. Nearly 60% of SAEs counted in articles and 41% in trial summaries had no description. Most cases of death (62.3%) and suicide (53.3%) were not reported in articles. Half or more of the 142 pairs were discordant in reporting the number (49.3%) or description (67.6%) of SAEs. These discrepancies resulted from journal articles’ (1) omission of complete SAE data, (2) reporting acute phase study results only and (3) more restrictive reporting criteria. Trial summaries with zero SAE were 2.35 (95% CI, 1.58 to 3.49; p<0.001) times more likely to be published with no discrepancy in their associated journal article. Since clinicalstudyresults.org was removed from the Internet in 2011, only 7.8% of retrieved trial summaries appear with results on clinicaltrials.gov. Conclusions Substantial discrepancies exist in SAE data found in journal articles and registered summaries of antidepressant and antipsychotic drug trials. Two main scientific sources accessible to clinicians and researchers are limited by incomplete, ambiguous and inconsistent reporting. Access to

  16. Transcriptomics and the mechanisms of antidepressant efficacy.

    PubMed

    Hodgson, Karen; Tansey, Katherine E; Powell, Timothy R; Coppola, Giovanni; Uher, Rudolf; Zvezdana Dernovšek, Mojca; Mors, Ole; Hauser, Joanna; Souery, Daniel; Maier, Wolfgang; Henigsberg, Neven; Rietschel, Marcella; Placentino, Anna; Aitchison, Katherine J; Craig, Ian W; Farmer, Anne E; Breen, Gerome; McGuffin, Peter; Dobson, Richard

    2016-01-01

    The mechanisms by which antidepressants have their effects are not clear and the reasons for variability in treatment outcomes are also unknown. However, there is evidence from candidate gene research that indicates gene expression changes may be involved in antidepressant action. In this study, we examined antidepressant-induced alterations in gene expression on a transcriptome-wide scale, exploring associations with treatment response. Blood samples were taken from a subset of depressed patients from the GENDEP study (n=136) before and after eight weeks of treatment with either escitalopram or nortriptyline. Transcriptomic data were obtained from these samples using Illumina HumanHT-12 v4 Expression BeadChip microarrays. When analysing individual genes, we observed that changes in the expression of two genes (MMP28 and KXD1) were associated with better response to nortriptyline. Considering connectivity between genes, we identified modules of genes that were highly coexpressed. In the whole sample, changes in one of the ten identified coexpression modules showed significant correlation with treatment response (cor=0.27, p=0.0029). Using transcriptomic approaches, we have identified gene expression correlates of the therapeutic effects of antidepressants, highlighting possible molecular pathways involved in efficacious antidepressant treatment. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  17. An Open Trial of Intensive Family Based Cognitive-Behavioral Therapy in Youth with Obsessive-Compulsive Disorder Who Are Medication Partial Responders or Nonresponders

    ERIC Educational Resources Information Center

    Storch, Eric A.; Lehmkuhl, Heather D.; Ricketts, Emily; Geffken, Gary R.; Marien, Wendi; Murphy, Tanya K.

    2010-01-01

    This study reports an open-trial of family-based cognitive-behavioral therapy (CBT) in children and adolescents with obsessive-compulsive disorder (OCD). Thirty primarily Caucasian youth with OCD (range = 7-19 years; 15 girls) who were partial responders or nonresponders to two or more medication trials that were delivered either serially or…

  18. Visual Motor Integration as a Screener for Responders and Non-Responders in Preschool and Early School Years: Implications for Inclusive Assessment in Oman

    ERIC Educational Resources Information Center

    Emam, Mahmoud Mohamed; Kazem, Ali Mahdi

    2016-01-01

    Visual motor integration (VMI) is the ability of the eyes and hands to work together in smooth, efficient patterns. In Oman, there are few effective methods to assess VMI skills in children in inclusive settings. The current study investigated the performance of preschool and early school years responders and non-responders on a VMI test. The full…

  19. An Open Trial of Intensive Family Based Cognitive-Behavioral Therapy in Youth with Obsessive-Compulsive Disorder Who Are Medication Partial Responders or Nonresponders

    ERIC Educational Resources Information Center

    Storch, Eric A.; Lehmkuhl, Heather D.; Ricketts, Emily; Geffken, Gary R.; Marien, Wendi; Murphy, Tanya K.

    2010-01-01

    This study reports an open-trial of family-based cognitive-behavioral therapy (CBT) in children and adolescents with obsessive-compulsive disorder (OCD). Thirty primarily Caucasian youth with OCD (range = 7-19 years; 15 girls) who were partial responders or nonresponders to two or more medication trials that were delivered either serially or…

  20. Visual Motor Integration as a Screener for Responders and Non-Responders in Preschool and Early School Years: Implications for Inclusive Assessment in Oman

    ERIC Educational Resources Information Center

    Emam, Mahmoud Mohamed; Kazem, Ali Mahdi

    2016-01-01

    Visual motor integration (VMI) is the ability of the eyes and hands to work together in smooth, efficient patterns. In Oman, there are few effective methods to assess VMI skills in children in inclusive settings. The current study investigated the performance of preschool and early school years responders and non-responders on a VMI test. The full…

  1. Involvement of AMPA receptors in the antidepressant-like effects of dextromethorphan in mice.

    PubMed

    Nguyen, Linda; Matsumoto, Rae R

    2015-12-15

    Dextromethorphan (DM) is an antitussive with rapid acting antidepressant potential based on pharmacodynamic similarities to ketamine. Building upon our previous finding that DM produces antidepressant-like effects in the mouse forced swim test (FST), the present study aimed to establish the antidepressant-like actions of DM in the tail suspension test (TST), another well-established model predictive of antidepressant efficacy. Additionally, using the TST and FST, we investigated the role of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors in the antidepressant-like properties of DM because accumulating evidence suggests that AMPA receptors play an important role in the pathophysiology of depression and may contribute to the efficacy of antidepressant medications, including that of ketamine. We found that DM displays antidepressant-like effects in the TST similar to the conventional and fast acting antidepressants characterized by imipramine and ketamine, respectively. Moreover, decreasing the first-pass metabolism of DM by concomitant administration of quinidine (CYP2D6 inhibitor) potentiated antidepressant-like actions, implying DM itself has antidepressant efficacy. Finally, in both the TST and FST, pretreatment with the AMPA receptor antagonist NBQX (2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide) significantly attenuated the antidepressant-like behavior elicited by DM. Together, the data show that DM exerts antidepressant-like actions through AMPA receptors, further suggesting DM may act as a safe and effective fast acting antidepressant drug.

  2. Amygdala Reactivity to Emotional Faces in the Prediction of General and Medication-Specific Responses to Antidepressant Treatment in the Randomized iSPOT-D Trial

    PubMed Central

    Williams, Leanne M; Korgaonkar, Mayuresh S; Song, Yun C; Paton, Rebecca; Eagles, Sarah; Goldstein-Piekarski, Andrea; Grieve, Stuart M; Harris, Anthony W F; Usherwood, Tim; Etkin, Amit

    2015-01-01

    Although the cost of poor treatment outcomes of depression is staggering, we do not yet have clinically useful methods for selecting the most effective antidepressant for each depressed person. Emotional brain activation is altered in major depressive disorder (MDD) and implicated in treatment response. Identifying which aspects of emotional brain activation are predictive of general and specific responses to antidepressants may help clinicians and patients when making treatment decisions. We examined whether amygdala activation probed by emotion stimuli is a general or differential predictor of response to three commonly prescribed antidepressants, using functional magnetic resonance imaging (fMRI). A test–retest design was used to assess patients with MDD in an academic setting as part of the International Study to Predict Optimized Treatment in Depression. A total of 80 MDD outpatients were scanned prior to treatment and 8 weeks after randomization to the selective serotonin reuptake inhibitors escitalopram and sertraline and the serotonin–norepinephrine reuptake inhibitor, venlafaxine-extended release (XR). A total of 34 matched controls were scanned at the same timepoints. We quantified the blood oxygen level-dependent signal of the amygdala during subliminal and supraliminal viewing of facial expressions of emotion. Response to treatment was defined by ⩾50% symptom improvement on the 17-item Hamilton Depression Rating Scale. Pre-treatment amygdala hypo-reactivity to subliminal happy and threat was a general predictor of treatment response, regardless of medication type (Cohen's d effect size 0.63 to 0.77; classification accuracy, 75%). Responders showed hypo-reactivity compared to controls at baseline, and an increase toward ‘normalization' post-treatment. Pre-treatment amygdala reactivity to subliminal sadness was a differential moderator of non-response to venlafaxine-XR (Cohen's d effect size 1.5; classification accuracy, 81%). Non-responders to

  3. The pharmacological properties of antidepressants.

    PubMed

    Racagni, Giorgio; Popoli, Maurizio

    2010-05-01

    Antidepressant drugs represent one of the main forms of effective treatment for the amelioration of depressive symptoms. Most available antidepressants increase extracellular levels of monoamines. However, it is now recognized that monoamine levels and availability are only part of the story, and that antidepressants whose mechanism of action is mainly based on the modulation of monoaminergic systems may not be able to satisfy the unmet needs of depression. Therefore, a number of compounds, developed for their potential antidepressant activity, are endowed with putative mechanisms of action not affecting traditional monoamine targets. This article briefly reviews, within a mechanistic perspective, the pharmacological profiles of representative antidepressants from each class, including monoamine oxidase inhibitors, tricyclics, norepinephrine reuptake inhibitors, selective serotonin reuptake inhibitors, norepinephrine and serotonin reuptake inhibitors, antidepressants interacting with dopaminergic, melatonergic, glutamatergic, or neuropeptide systems. The undesirable side effects of currently used antidepressants, which can often be a reason for lack of compliance, are also considered.

  4. Response prediction to antidepressants using scalp and source-localized loudness dependence of auditory evoked potential (LDAEP) slopes.

    PubMed

    Jaworska, Natalia; Blondeau, Claude; Tessier, Pierre; Norris, Sandhaya; Fusee, Wendy; Blier, Pierre; Knott, Verner

    2013-07-01

    The loudness-dependence of the auditory evoked potential (LDAEP) slope may be inversely related to serotonin (5-HT) neurotransmission. Thus, steep LDAEPs tend to predict a positive response to selective serotonin reuptake inhibitor (SSRI) antidepressants, which augment 5-HT. However, LDAEPs also predict outcome to antidepressants indirectly altering 5-HT (e.g. bupropion). Hence, the LDAEP's predicative specificity and sensitivity to antidepressant response/outcome remains elusive. Scalp N1, P2 and N1/P2 LDAEP slopes and standardized low resolution brain electromagnetic tomography (sLORETA)-localized N1 and P2 LDAEP slopes were assessed in depressed individuals (N=51) at baseline, 1 and 12 weeks post-treatment with one of three antidepressant regimens [escitalopram (ESC)+bupropion (BUP), ESC or BUP]. Clinical response was greatest with ESC+BUP at week 1. Treatment responders had steep N1 sLORETA-LDAEP baseline slopes while non-responders had shallow ones. P2 sLORETA-LDAEP slope increases at 1 week existed in responders; decreases were noted in non-responders. Exploratory analyses indicated that more BUP and ESC responders versus non-responders had steep baseline N1 sLORETA-LDAEP slopes. Additionally, slight decreases in scalp P2 LDAEP by week 1 existed for ESC treatment, while slope increases existed with ESC+BUP treatment. Only baseline N1 sLORETA-LDAEP discriminated treatment responders/non-responders. This work confirms that certain LDAEP measures are associated with treatment outcome and appear to be differentially modulated with varying antidepressant drug regimens, though this should be confirmed using larger samples. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Ketamine and other potential glutamate antidepressants.

    PubMed

    Dutta, Arpan; McKie, Shane; Deakin, J F William

    2015-01-30

    The need for rapid acting antidepressants is widely recognised. There has been much interest in glutamate mechanisms in major depressive disorder (MDD) as a promising target for the development of new antidepressants. A single intravenous infusion of ketamine, a N-methyl-d-aspartate (NMDA) receptor antagonist anaesthetic agent, can alleviate depressive symptoms in patients within hours of administration. The mechanism of action appears to be in part through glutamate release onto non-NMDA receptors including α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and metabotropic receptors. However these are also reported effects on 5-HT, dopamine and intracellular effects on the mammalian target of rapamycin (mTOR) pathway. The effects of SSRI (Selective Serotonin Reuptake Inhibitor) antidepressants may also involve alterations in NMDA function. The article reviews the effect of current antidepressants on NMDA and examines the efficacy and mechanism of ketamine. Response to ketamine is also discussed and comparison with other glutamate drugs including lamotrigine, amantadine, riluzole, memantine, traxoprodil, GLYX-13, MK-0657, RO4917523, AZD2066 and Coluracetam. Future studies need to link the rapid antidepressant effects seen with ketamine to inflammatory theories in MDD.

  6. The antidepressant effects of anticholinergic drugs.

    PubMed

    Howland, Robert H

    2009-06-01

    Acetylcholine is a neurotransmitter that is important for communication between neurons and muscle, is involved in direct neurotransmission in the autonomic parasympathetic nervous system, and has been implicated in cognitive processing, arousal, and attention in the brain. The cholinergic-adrenergic hypothesis of mood disorders states that a given affective state might represent a balance between central cholinergic and adrenergic neurotransmitter activity in those areas of the brain regulating moods. According to this hypothesis, depression would be the clinical manifestation of a state of cholinergic dominance, whereas mania would reflect adrenergic dominance. On the basis of this hypothesis, anticholinergic drugs have been investigated as potential treatments for depression, but study results have not shown consistent antidepressant effects. However, the dosage dependency of scopolamine's effect across different studies and the lack of antidepressant effects with other anticholinergic drugs suggest that a specific muscarinic receptor subtype might be most relevant to the potential antidepressant mechanism of action of anticholinergic drugs.

  7. Antidepressants modulate glycine action in rat hippocampus

    PubMed Central

    Chang, Hyun-Kyung; Kim, Khae Hawn; Kang, Ki-Woon; Kang, Yoo-Jin; Kim, Tae-Wook; Park, Hun-Kyung; Kim, Sung-Eun; Kim, Chang-Ju

    2015-01-01

    Antidepressants are drugs that relieve symptoms of depressive disorders. Fluoxetine, tianeptine, and milnacipran are different types of antidepressants, and they have widely been used for relieving of depression symptoms. In the present study, the effects of fluoxetine, tianeptine, and milnacipran on the glycine-induced ion current by nystatin-perforated patch clamp and on the amplitude of field potential in the hippocampal CA1 region by multichannel extracellular recording, MED64, system, were studied. In the present results, fluoxetine, tianeptine, and milnacipran reduced glycine-induced ion current in the hippocampal CA1 neurons in nystatin-perforated patch clamp method. These drugs enhanced the amplitude of the field potential in the hippocampal CA1 region in MED64 system. These results suggest that antidepressants may increase neuronal activity by enhancing field potential through inhibition on glycine-induced ion current. PMID:26730381

  8. Antidepressants modulate glycine action in rat hippocampus.

    PubMed

    Chang, Hyun-Kyung; Kim, Khae Hawn; Kang, Ki-Woon; Kang, Yoo-Jin; Kim, Tae-Wook; Park, Hun-Kyung; Kim, Sung-Eun; Kim, Chang-Ju

    2015-12-01

    Antidepressants are drugs that relieve symptoms of depressive disorders. Fluoxetine, tianeptine, and milnacipran are different types of antidepressants, and they have widely been used for relieving of depression symptoms. In the present study, the effects of fluoxetine, tianeptine, and milnacipran on the glycine-induced ion current by nystatin-perforated patch clamp and on the amplitude of field potential in the hippocampal CA1 region by multichannel extracellular recording, MED64, system, were studied. In the present results, fluoxetine, tianeptine, and milnacipran reduced glycine-induced ion current in the hippocampal CA1 neurons in nystatin-perforated patch clamp method. These drugs enhanced the amplitude of the field potential in the hippocampal CA1 region in MED64 system. These results suggest that antidepressants may increase neuronal activity by enhancing field potential through inhibition on glycine-induced ion current.

  9. Synthesis and Behavioral Studies of Chiral Cyclopropanes as Selective α4β2-Nicotinic Acetylcholine Receptor Partial Agonists Exhibiting an Antidepressant Profile. Part III.

    PubMed

    Onajole, Oluseye K; Vallerini, Gian Paolo; Eaton, J Brek; Lukas, Ronald J; Brunner, Dani; Caldarone, Barbara J; Kozikowski, Alan P

    2016-06-15

    We report the synthesis and biological characterization of novel derivatives of 3-[(1-methyl-2(S)-pyrrolidinyl)methoxy]-5-cyclopropylpyridine (4a-f and 5) as potent and highly selective α4β2-nicotinic acetylcholine receptor (nAChR) full or partial agonists. A systematic structure-activity study was carried out on the previously described compound 3b, particularly concerning its (2-methoxyethyl)cyclopropyl side-chain, in an effort to improve its metabolic stability while maintaining receptor selectivity. Compound 4d exhibited very similar subnanomolar binding affinity for α4β2- and α4β2*-nAChRs compared to 3b, and it showed excellent potency in activating high-sensitivity (HS) α4β2-nAChRs with an EC50 value of 8.2 nM. Testing of 4d in the SmartCube assay revealed that the compound has a combined antidepressant plus antipsychotic signature. In the forced swim test at a dose of 30 mg/kg given intraperitoneally, 4d was found to be as efficacious as sertraline, thus providing evidence of the potential use of the compound as an antidepressant. Additional promise for use of 4d in humans comes from pharmacokinetic studies in mice indicating brain penetration, and additional assays show compound stability in the presence of human microsomes and hepatocytes. Thus, 4d has a very favorable preclinical drug profile.

  10. A comparison between adsorption mechanism of tricyclic antidepressants on silver nanoparticles and binding modes on receptors. Surface-enhanced Raman spectroscopy studies.

    PubMed

    Jaworska, Aleksandra; Malek, Kamilla

    2014-10-01

    A series of the tricyclic antidepressants known as a surface-active drugs, has been used as a model for an evaluation of their adsorption mechanism on the metal substrate and its relationship to pharmacological action of the chosen drugs. In these studies, six antidepressants were adsorbed on the metal substrate in a form of silver nanoparticles (ca. 30 nm in diameter) and afterwards their interactions have been examined in terms of surface-enhanced Raman spectroscopy (SERS). An analysis of SERS spectra has revealed that the dibenzopine moiety is a primary site of the adsorption with some differences in the orientation with respect to the metal among the studied molecules. The spectral changes due to the interactions with the silver particles also appear in the region typical for vibrations of the side chain. These observations are consistent with a model, in which the tricyclic ring is docked in the outer vestibule of biogenic amine transporters whereas the dimethyl-aminopropyl side chain is pointed to the substrate binding site. This work sheds a light on a potential of SERS technique in predicting a key functional group responsible for drug action. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. SSRI antidepressants: altered psychomotor development following exposure in utero?

    PubMed

    2013-02-01

    Selective serotonin reuptake inhibitor antidepressants (SSRIs) are sometimes prescribed to pregnant women. The potential consequences for the unborn child are gradually becoming clearer. In a case-control study of 298 children with autism and 1507 controls, 6.7% of mothers of autistic children had been prescribed an antidepressant during the year before delivery, compared to 3.3% of control mothers. The antidepressant was usually an SSRI. A dozen other small epidemiological studies of neurological development in children exposed to antidepressants in utero have provided mixed results. Two of these studies suggested a risk of psychomotor retardation. In practice, SSRI antidepressants should only be considered for pregnant women when non-drug measures fail and when symptoms are sufficiently serious to warrant drug therapy.

  12. Depression, Antidepressants, and Neurogenesis: A Critical Reappraisal

    PubMed Central

    Hanson, Nicola D; Owens, Michael J; Nemeroff, Charles B

    2011-01-01

    The neurogenesis hypothesis of depression posits (1) that neurogenesis in the subgranular zone of the dentate gyrus is regulated negatively by stressful experiences and positively by treatment with antidepressant drugs and (2) that alterations in the rate of neurogenesis play a fundamental role in the pathology and treatment of major depression. This hypothesis is supported by important experimental observations, but is challenged by equally compelling contradictory reports. This review summarizes the phenomenon of adult hippocampal neurogenesis, the initial and continued evidence leading to the development of the neurogenesis hypothesis of depression, and the recent studies that have disputed and/or qualified those findings, to conclude that it can be affected by stress and antidepressants under certain conditions, but that these effects do not appear in all cases of psychological stress, depression, and antidepressant treatment. PMID:21937982

  13. An investigation of EEG, genetic and cognitive markers of treatment response to antidepressant medication in patients with major depressive disorder: a pilot study.

    PubMed

    Spronk, D; Arns, M; Barnett, K J; Cooper, N J; Gordon, E

    2011-01-01

    The aim of this study was to investigate if biomarkers in QEEG, genetic and neuropsychological measures are suitable for the prediction of antidepressant treatment outcome in depression. Twenty-five patients diagnosed with major depressive disorder were assessed twice, pretreatment and at 8-wk follow-up, on a variety of QEEG and neuropsychological tasks. Additionally, cheek swab samples were collected to assess genetic predictors of treatment outcome. The primary outcome measure was the absolute decrease on the HAM-D rating scale. Regression models were built in order to investigate which markers contribute most to the decrease in absolute HAM-D scores. Patients who had a better clinical outcome were characterized by a decrease in the amplitude of the Auditory Oddball N1 at baseline. The 'Met/Met' variant of the COMT gene was the best genetic predictor of treatment outcome. Impaired verbal memory performance was the best cognitive predictor. Raised frontal Theta power was the best EEG predictor of change in HAM-D scores. A tentative integrative model showed that a combination of N1 amplitude at Pz and verbal memory performance accounted for the largest part of the explained variance. These markers may serve as new biomarkers suitable for the prediction of antidepressant treatment outcome.

  14. Abuse and misuse of antidepressants

    PubMed Central

    Evans, Elizabeth A; Sullivan, Maria A

    2014-01-01

    Background Rates of prescription drug abuse have reached epidemic proportions. Large-scale epidemiologic surveys of this under-recognized clinical problem have not included antidepressants despite their contribution to morbidity and mortality. The purpose of this review is to look specifically at the misuse of antidepressants and how this behavior may fit into the growing crisis of nonmedical use of prescription drugs. Methods We conducted a comprehensive search on PubMed, Medline, and PsycINFO using the search terms “antidepressant”, “abuse”, “misuse”, “nonmedical use”, “dependence”, and “addiction”, as well as individual antidepressant classes (eg, “SSRI”) and individual antidepressants (eg, “fluoxetine”) in various combinations, to identify articles of antidepressant misuse and abuse. Results A small but growing literature on the misuse and abuse of antidepressants consists largely of case reports. Most cases of antidepressant abuse have occurred in individuals with comorbid substance use and mood disorders. The most commonly reported motivation for abuse is to achieve a psychostimulant-like effect. Antidepressants are abused at high doses and via a variety of routes of administration (eg, intranasal, intravenous). Negative consequences vary based upon antidepressant class and pharmacology, but these have included seizures, confusion, and psychotic-like symptoms. Conclusion The majority of individuals prescribed antidepressants do not misuse the medication. However, certain classes of antidepressants do carry abuse potential. Vulnerable patient populations include those with a history of substance abuse and those in controlled environments. Warning signs include the presence of aberrant behaviors. Physicians should include antidepressants when screening for risky prescription medication use. When antidepressant misuse is detected, a thoughtful treatment plan, including referral to an addiction specialist, should be developed and

  15. Suboptimal antidepressant use in the elderly.

    PubMed

    Wang, Philip S; Schneeweiss, Sebastian; Brookhart, M Alan; Glynn, Robert J; Mogun, Helen; Patrick, Amanda R; Avorn, Jerry

    2005-04-01

    Ongoing changes in available agents and health care delivery systems have made it imperative to study the quality of antidepressant use in vulnerable and traditionally underserved elderly. We conducted a retrospective cohort study among 12,130 new antidepressant users aged > or =65 years with a recent diagnosis of depression in the Pennsylvania Pharmaceutical Assistance Contract for the Elderly Program from January 1, 1994, to December 31, 1999. Additional use information was available through Medicare data. Potentially hazardous antidepressant regimens were defined as use of highly anticholinergic agents or daily dosages in excess of geriatric prescribing guidelines. Low-intensity regimens were defined by lower than recommended daily dosages, too-short durations of therapy, or lack of follow-up. Of all elderly antidepressant users, 43.3% were taking suboptimal regimens. Potentially hazardous regimens were used by 11.9%, including 7.3% taking highly anticholinergic agents and 5.3% using excessively high daily dosages. Low-intensity regimens were used by 34.8% of patients, including 7.6% with excessively low daily dosages, 19.3% with short durations of therapy, and 14.8% with inadequate follow-up. Potentially hazardous regimens were associated with ages 65 to 74 years, nursing home residence, cancer diagnoses, less comorbidity, use of other psychiatric medications, making more physician visits, and earlier calendar years. Low-intensity regimens were associated with ages > or =85 years, nonwhite race, greater comorbidity, fewer physician visits or inpatient days in the baseline 6 months, and not using other psychiatric medications. Suboptimal antidepressant use remains common in the elderly, especially the use of inadequately intensive regimens. Interventions are needed to improve the quality and outcomes of antidepressant use in this vulnerable population.

  16. [Antidepressants in migraine prophylaxis].

    PubMed

    Nagata, Eiichiro

    2009-10-01

    The initiation of a prophylactic treatment for migraine depends on the frequency of migraine attacks and the extent of the function disability associated with these attacks. Antidepressants have good evidence of efficacy in the prophylactic treatment for migraine. In general, among the antidepressants, amitriptyline is the most frequently prescribed by headache specialists. Several clinical trials on this drug have also evidenced the remarkable benefits of amitriptyline in the prophylactic treatment of migraine attack. In evidence-based guidelines developed by Japanese Headache Society and American Neurological Association, it is classified as a Group 1 drugs (effective drug for the prevention of migraine attack). Moreover, these drugs are more useful in cases where there is comorbidity with conditions such as depression. The side-effects of these drugs are sleepiness and dry mouth. Administration of amytriptyline at low dose can reduce the frequency of side effects such as sleepiness.

  17. Antidepressants for people with epilepsy and depression.

    PubMed

    Maguire, Melissa J; Weston, Jennifer; Singh, Jasvinder; Marson, Anthony G

    2014-12-03

    Depressive disorders are the most common psychiatric comorbidity in patients with epilepsy, affecting around one-third, with a significant negative impact on quality of life. There is concern that patients may not be receiving appropriate treatment for their depression because of uncertainty regarding which antidepressant or class works best and the perceived risk of exacerbating seizures. This review aims to address these issues and inform clinical practice and future research. We aimed to review and synthesise evidence from randomised controlled trials of antidepressants and prospective non-randomised studies of antidepressants used for treating depression in patients with epilepsy. The primary objectives were to evaluate the efficacy and safety of antidepressants in treating depressive symptoms and the effect on seizure recurrence. We conducted a search of the following databases: the Cochrane Epilepsy Group Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL 2014, Issue 5), MEDLINE (Ovid), SCOPUS, PsycINFO, www.clinicaltrials.gov and conference proceedings, including studies published up to 31 May 2014. There were no language restrictions. We included randomised controlled trials (RCTs) and prospective non-randomised cohort controlled and uncontrolled studies investigating children or adults with epilepsy treated with an antidepressant for depressive symptoms. The intervention group consisted of patients receiving an antidepressant drug in addition to an existing antiepileptic drug regimen. The control group(s) consisted of patients receiving a placebo, comparative antidepressant, psychotherapy or no treatment in addition to an existing antiepileptic drug regimen. We extracted data on trial design factors, patient demographics and outcomes for each study. The primary outcomes were changes in depression scores (proportion with a greater than 50% improvement or mean difference) and change in seizure frequency (mean difference or

  18. The change of prefrontal QEEG theta cordance as a predictor of response to bupropion treatment in patients who had failed to respond to previous antidepressant treatments.

    PubMed

    Bares, Martin; Brunovsky, Martin; Novak, Tomas; Kopecek, Miloslav; Stopkova, Pavla; Sos, Peter; Krajca, Vladimir; Höschl, Cyril

    2010-07-01

    The aim of the study was to examine whether the reduction of theta prefrontal quantitative EEG (QEEG) cordance after one week of bupropion administration is a predictor of response to a 4-week treatment in patients that had failed to respond to previous antidepressant treatments. EEG data of 18 inpatients were monitored at baseline and after one week. QEEG cordance was computed at 3 frontal electrodes (Fp1, Fp2, Fz). Response to treatment was defined as a >/=50% reduction of MADRS score. Nine of the eleven responders and one of the seven non-responders showed decreased prefrontal cordance value after the first week of treatment (p=0.01). Positive and negative predictive values of cordance reduction for the prediction of response to the treatment were 0.9 and 0.75, respectively. Similar to other antidepressants, the reduction of prefrontal QEEG cordance might be helpful in the prediction of the acute outcome of bupropion treatment. Copyright 2010 Elsevier B.V. and ECNP. All rights reserved.

  19. Potential Antidepressant Constituents of Nigella sativa Seeds

    PubMed Central

    Elkhayat, Ehab S.; Alorainy, Mohammad S.; El-Ashmawy, Ibrahim M.; Fat’hi, Shawkat

    2016-01-01

    Background: Nigella sativa Linn. is well known seed in the Middle East, Asia, and the Far East as a natural remedy for many ailments and as a flavoring agent proclaimed medicinal usage dating back to the ancient Egyptians, Greeks, and Romans. An authentic saying of the Prophet Muhammad (Peace Be Upon Him) about black seed is also quoted in Al-Bukhari. Objective: This study was carried out to evaluate the antidepressant effect and isolate the potential antidepressant constituents of the polar extract of N. sativa seeds. Materials and Methods: The antidepressant effect was evaluated through the immobility duration in tail suspension and forced swim tests (FSTs). Albino mice were orally treated with N. sativa polar extract and its RP-18 column chromatography fractions (50 and 100 mg/kg,). Results: The polar extract and two of its sub-fractions were significantly able to decrease the immobility time of mice when subjected to both tail suspension and FSTs, the effects are comparable to standard drug (Sertraline, 5 mg/kg). However, these treatments did not affect the number of crossings and rearing in the open field test. Phytochemical investigation of the two active fractions led to the isolation of quercetin-3-O-α-L-rhamnopyranoside 1, quercetin-7-O-β-D-gluco- pyranoside 2, tauroside E 3, and sapindoside B as the potential antidepressant constituents. SUMMARY Phytochemical and biological evaluation the antidepressant constituents in Nigella sativa using the tail suspension and forced swim methods afforded the isolation and identification of quercetin-3-O-α-L rhamnopyranoside, quercetin-7-O-β-D gluco pyranoside, tauroside E, and sapindoside B as the potential antidepressant constituents in the polar extract of N. sativa. The isolated compounds were identified through extensive NMR analysis (1D, 2D, ESI MS). Abbreviations used: TST: Tail suspension test, FST: Forced swim test, OFT: An Open field test PMID:27041854

  20. Milnacipran versus other antidepressive agents for depression.

    PubMed

    Nakagawa, Atsuo; Watanabe, Norio; Omori, Ichiro M; Barbui, Corrado; Cipriani, Andrea; McGuire, Hugh; Churchill, Rachel; Furukawa, Toshi A

    2009-07-08

    Although pharmacological and psychological interventions are both effective for major depression, antidepressant drugs are frequently used as first-line treatment in primary and secondary care settings. Milnacipran, a dual serotonin-norepinephrine reuptake inhibitor (SNRI), is one of the antidepressant drugs that clinicians use for routine depression care. To assess the evidence for the efficacy, acceptability and tolerability of milnacipran in comparison with tricyclic antidepressants (TCAs), heterocyclics, SSRIs and other newer antidepressive agents in the acute-phase treatment of major depression. The Cochrane Collaboration Depression, Anxiety & Neurosis review group Controlled Trials Register (CCDANCTR-Studies and CCDANCTR-References) were electronically searched in August 2008. References of relevant trials and other reviews were also checked. Trial databases of the drug-approving agencies and ongoing clinical trial registers for all published and unpublished trials were hand-searched in 2007. All relevant authors were contacted for supplemental data. No language restriction was applied. Randomised controlled trials comparing milnacipran with any other active antidepressive agents (including non-conventional agents such as herbal products like hypericum) as monotherapy in the acute phase of major depression were selected. Two reviewers independently checked eligibility, assessed methodological quality and extracted data from the eligible trials using a standardised data extraction form. The number of participants who responded to treatment or those who achieved remission were calculated on an intention-to-treat basis. Random-effects meta-analyses were conducted, combining data from the included trials. A total of 16 randomised controlled trials (n=2277) were included in the meta-analysis.Despite the size of this sample, the pooled 95% confidence intervals were rather wide and there were no statistically significant differences in efficacy, acceptability and

  1. "It doesn't do any harm, but patients feel better": a qualitative exploratory study on gastroenterologists' perspectives on the role of antidepressants in inflammatory bowel disease

    PubMed Central

    Mikocka-Walus, Antonina A; Turnbull, Deborah A; Moulding, Nicole T; Wilson, Ian G; Andrews, Jane M; Holtmann, Gerald J

    2007-01-01

    Background Interest in psychological factors in patients with inflammatory bowel disease (IBD) has increased in recent years. It has even been proposed that treating psychological co-morbidities with antidepressants may control disease activity and improve quality of life. Despite this, there is no data on gastroenterologists' attitudes to, and experiences with, antidepressant therapy in patients with IBD. Methods We conducted semi-structured interviews with 18 gastroenterologists associated with metropolitan teaching hospitals. Qualitative content analysis was used to examine their responses. Results Seventy-eight percent of gastroenterologists had treated IBD patients with antidepressants for pain, depression and/or anxiety, and insomnia. Antidepressants were reported to be useful in improving psychosocial well-being, quality of life, and self-management of the disease by patients. However, in this group of gastroenterologists, there appears to be skepticism towards psychological disorders themselves or antidepressant therapy having a central role in either the causation of IBD or its clinical course. Nevertheless, these gastroenterologists were receptive to the idea of conducting a trial of the role of antidepressants in IBD. Conclusion While the majority of specialists have treated IBD patients with antidepressants, there is considerable skepticism with regard to efficacy of antidepressive therapy or the role of psychological factors in the outcome of IBD patients. PMID:17892587

  2. Efficacy and safety of adjunctive cariprazine in inadequate responders to antidepressants: a randomized, double-blind, placebo-controlled study in adult patients with major depressive disorder.

    PubMed

    Durgam, Suresh; Earley, Willie; Guo, Hua; Li, Dayong; Németh, György; Laszlovszky, István; Fava, Maurizio; Montgomery, Stuart A

    2016-03-01

    Cariprazine is an atypical antipsychotic currently under investigation as adjunctive therapy in patients with major depressive disorder (MDD) who have inadequate response to standard antidepressant therapy. A randomized, double-blind, placebo-controlled, flexible-dose study was conducted from December 2011 to December 2013 in adults who met DSM-IV-TR criteria for MDD and had an inadequate antidepressant response. Eligible patients were randomized to 8-week adjunctive treatment with placebo (n = 269), cariprazine 1-2 mg/d (n = 274), or cariprazine 2-4.5 mg/d (n = 276). The primary efficacy parameter was change from baseline to week 8 in Montgomery-Asberg Depression Rating Scale (MADRS) total score; P values were adjusted for multiple comparisons. Safety assessments included adverse events, clinical laboratory tests, vital signs, electrocardiograms (ECGs), and suicidality. Compared with placebo, reduction in MADRS total score at week 8 was significantly greater with adjunctive cariprazine 2-4.5 mg/d (least squares mean difference [LSMD] = -2.2; adjusted P = .0114), but not with cariprazine 1-2 mg/d (LSMD = -0.9; adjusted P = .2404). Significant LSMDs for MADRS total score change were detected at all earlier study visits (weeks 2, 4, 6) in the 2- to 4.5-mg/d group and at weeks 2 and 4 in the 1- to 2-mg/d group (all P values < .05). Treatment-emergent adverse events reported in ≥ 10% of patients in either cariprazine dosage group were akathisia (22.3%), insomnia (13.6%), and nausea (12.8%) (all in 2- to 4.5-mg/d group). Mean changes in metabolic parameters, vital signs, and ECG parameters were generally similar between groups. No suicide-related adverse events were reported. These results show that adjunctive cariprazine 2-4.5 mg/d was effective and generally well tolerated in adults with MDD who had inadequate responses to standard antidepressants. Further clinical studies to confirm these results are warranted. ClinicalTrials.gov identifier: NCT01469377.

  3. [Antidepressants consumption in the global population in France].

    PubMed

    Olié, J P; Elomari, F; Spadone, C; Lépine, J P

    2002-01-01

    The consumption of antidepressant seems to be in France higher than in comparable countries, as well as the overall consumption of healthcare and medications. In Western countries, in recent years, the use of antidepressants has regularly increased, mainly due to the use of serotoninergic antidepressants. In France, in a week, the prevalence of antidepressant use in the overall population increased from 1.7% in 1992 to 3% in 1995. This survey addressed the overall population in the form of a representative sample focusing on subjects who indicated, at the time they were consulted, that they were taking an antidepressant. The study aimed to determine the circumstances of prescription: prescriber file, reason for prescription, type of medication prescribed, match between the prescription and the product indications stated in the marketing authorization, prescription duration and reason for discontinuing treatment. Methodology - The first stage consisted in forwarding a letter to a panel of 44 000 subjects aged 15 years or more and representative of the French population. The aim was to achieve a cross-sectional description of the population taking antidepressants. The response rate was 82% (36 036 subjects). The subjects who stated that they were taking an antidepressant were re-contacted by telephone by an interviewer trained in the use of the Composite International Diagnostic Interview - lifetime (CIDI), exploring depression and anxiety diseases with a view to potential diagnosis as per DSM criteria. Longitudinal follow-up over 8 months from the initial screening was evaluated using a monthly questionnaire on the time course of antidepressant consumption. Results - Out of 20 000 households, comprising 44 000 people aged over 15 years, 1 333 people were taking an antidepressant or had taken one in the previous 4 weeks. The sex ratio of the antidepressant consumers was 3 women to 1 man, amplifying the known sex ratio with respect to depressive disorders. The mean

  4. Experiences from consumer reports on psychiatric adverse drug reactions with antidepressant medication: a qualitative study of reports to a consumer association

    PubMed Central

    2012-01-01

    Background The new European pharmacovigilance legislation has been suggested as marking the beginning of a new chapter in drug safety, making patients an important part of pharmacovigilance. In Sweden since 2008 it has been possible for consumers to report adverse drug reactions (ADRs) to the Medical Products Agency (MPA), and these reports are now understood as an increasingly valuable contribution in the monitoring of safety aspects in medicines. Already in 2002 it was possible to report experiences with medicines to the non-profit and independent organization Consumer Association for Medicines and Health (KILEN) through a web-based report form with an opportunity to describe ADR experiences in free text comments. The aim of this study was to qualitatively analyze the free text comments appended to consumer reports on antidepressant medication. Methods All reports of suspected adverse reactions regarding antidepressant medications submitted from January 2002 to April 2009 to KILEN’s Internet-based reporting system in Sweden were analyzed according to reported narrative experience(s). Content analysis was used to interpret the content of 181 reports with free text comments. Results Three main categories emerged from the analyzed data material: (1) Experiences of drug treatment with subcategories (a) Severe psychiatric adverse reactions, and (b) Discontinuation symptoms; (2) Lack of communication and (3) Trust and distrust. A majority of the reports to KILEN were from patients experiencing symptoms of mental disturbances (sometimes severe) affecting them in many different ways, especially during discontinuation. Several report included narratives of patients not receiving information of potential ADRs from their doctor, but also that there were no follow-ups of the treatment. Trust was highlighted as especially important and some patients reported losing confidence in their doctor when they were not believed about the suspected ADRs they experienced, making them

  5. Stopping rules for surveys with multiple waves of nonrespondent follow-up.

    PubMed

    Rao, R Sowmya; Glickman, Mark E; Glynn, Robert J

    2008-05-30

    In surveys with multiple waves of follow-up, nonrespondents to the first wave are sometimes followed intensively but this does not guarantee an increase in the response rate or an appreciable change in the estimate of interest. Most prior research has focused on stopping rules for Phase I clinical trials. To our knowledge there are no standard methods to stop follow-up in observational studies. Previous research suggests optimal stopping strategies where decisions are based on achieving a given precision for minimum cost or reducing cost for a given precision. In this paper, we propose three stopping rules that are based on assessing whether successive waves of sampling provide evidence that the parameter of interest is changing. Two of the rules rely on examining patterns of observed responses while the third rule uses missing data methods to multiply impute missing responses. We also present results from a simulation study to evaluate our proposed methods. Our simulations suggest that rules that adjust for nonresponse are preferred for decisions to discontinue follow-up since they reduce bias in the estimate of interest. The rules are not complicated and may be applied in a straightforward manner. Discontinuing follow-up would save time and possibly resources, and adjusting for the nonresponse in the analysis would reduce the impact of nonresponse bias.

  6. Variation in response to short-term antidepressant treatment between patients with continuous and non-continuous cycling bipolar disorders.

    PubMed

    Tundo, Antonio; Calabrese, Joseph R; Proietti, Luca; de Fillippis, Rocco

    2015-03-15

    The study aimed to compare effectiveness and safety of short-term antidepressant treatment between patients with continuous (CCC) and non-continuous (N-CCC) cycling bipolar disorders. The study sample included 101 patients with bipolar disorder, 22 (21.8%) CCC and 79 (78.2%) N-CCC. Response was defined as a HDRS21 total score <7 at 12 weeks of treatment and remission as a ≥50% reduction of baseline HDRS21 total score sustained for 8 weeks. Compared with N-CCC patients, CCC patients achieved a significantly lower percentage of response (respectively 50% vs. 82.3%, χ²=9.6, p=0.002) and remission (respectively 40.9% vs. 69.6%, χ²=6.11, p=0.013). Adjusted logistic regression analysis indicated that CCC patients were 4.3 times more likely to be non-responders and 3.3 times more likely to be non-remitters than N-CCC patients. AD safety, 1 (5.0%) CCC patient committed a suicide attempt and AD-emerging switch was observed in 2 patients with N-CCC (2.5%) and in 1 with CCC (4.5%). The observational nature of the study, retrospective assessment of course, and unblinded outcomes assessment. Our findings indicate that the presence or absence of a free interval identifies two different forms of bipolar disorders with different response not only to prophylactic treatment, as previously reported, but also to short-term ADs. We submit that clinicians should take into consideration their patients׳ pattern of cycling when prescribing short-term AD treatment. Moreover, subtypes of bipolar disorders might be used as moderators of treatment response in studies assessing the efficacy or the effectiveness of antidepressant treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Antidepressants during pregnancy and postpartum hemorrhage: a systematic review.

    PubMed

    Bruning, Andrea H L; Heller, Hanna M; Kieviet, Noera; Bakker, Petra C A M; de Groot, Christianne J M; Dolman, Koert M; Honig, Adriaan

    2015-06-01

    The use of antidepressants in pregnancy is increasing. Concerns have risen about the use of antidepressants during pregnancy and the risk of postpartum hemorrhage (PPH). The aim of this systematic review is to summarize evidence on the association between use of antidepressants during pregnancy and the risk of PPH. An Embase and Pubmed search was conducted. English and Dutch language studies reporting original data regarding bleeding after delivery associated with exposure to antidepressants during pregnancy were selected. Quality appraisal was conducted using the Newcastle Ottawa Scale (NOS). Out of 81 citations, 4 studies were included. Based on the NOS, 3 were considered of good quality and 1 was considered of satisfactory quality. Two studies reported an increased incidence of PPH in women who used antidepressants during pregnancy. The other two studies identified no overall increased risk of PPH among pregnant women exposed to antidepressants. The existing evidence remains inconclusive whether use of antidepressants during pregnancy is associated with an increased risk of postpartum hemorrhage. If there is such an association the absolute increased risk will be low and the clinical relevance needs to be further examined. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Evaluation of anti-obesity activity of duloxetine in comparison with sibutramine along with its anti-depressant activity: an experimental study in obese rats.

    PubMed

    Chudasama, H P; Bhatt, P A

    2009-11-01

    5-HT and noradrenaline are important neurotransmitters that control increase in body mass and are involved in the pathophysiology of obesity and depression. Sibutramine, an established anti-obesity agent, and duloxetine, an anti-depressant agent, are serotonin noradrenaline reuptake inhibitors (SNRIs). The objective of the present study was to compare the anti-obesity effect of duloxetine with sibutramine along with its effect on blood pressure and depression in obese rats. The secondary objective of the study was to determine if a relationship exists between obesity and depression. Obesity was induced by high-fat diet (HFD) in healthy male Sprague-Dawley rats. After 5 weeks of feeding HFD, animals were overweight (17.57%) with high food intake (57.15%) in comparison with normal animals. These obese animals were treated with duloxetine (30 mg x kg(-1), p.o.) and sibutramine (5 mg x kg(-1), p.o.) for 4 weeks. Control animals were treated with duloxetine alone (30 mg x kg(-1), p.o.). Our results depict that duloxetine was as effective as sibutramine in reducing food intake, body mass, and relative adiposity, and increasing rectal temperature with an added advantage of decreasing blood pressure, which sibutramine failed to do. Besides reduction in body mass, unlike sibutramine, duloxetine improved depressive state as evaluated by despair swimming test, tail suspension test, and open field test, speculating its use as an anti-obesity agent in obese-depressive animals. Since obese control animals reflected decreased locomotor activity, a positive relationship can be speculated to exist between obesity and depression. Further studies on various antidepressant models are required to confirm this relationship.

  9. A Randomized, Placebo-Controlled Pilot Study of Quetiapine-XR Monotherapy or Adjunctive Therapy to Antidepressant in Acute Major Depressive Disorder with Current Generalized Anxiety Disorder

    PubMed Central

    Li, Ranran; Wu, Renrong; Chen, Jun; Kemp, David E.; Ren, Ming; Conroy, Carla; Chan, Philip; Serrano, Mary Beth; Ganocy, Stephen J.; Calabrese, Joseph R.; Gao, Keming

    2016-01-01

    Objectives To pilot efficacy and safety data of quetiapine-XR monotherapy or adjunctive therapy to antidepressant(s) in the acute treatment of MDD with current generalized anxiety disorder (GAD). Methods The Mini International Neuropsychiatric Interview was used to ascertain the diagnosis of DSM-IV Axis I disorders. Eligible patients were randomly assigned to quetiapine-XR or placebo for up to 8 weeks. Changes from baseline to endpoint in Hamilton Depression Rating Scale-17 items (HAMD-17), Hamilton Anxiety Rating Scale (HAM-A), Clinical Global Impression-Severity (CGI-S), Quick Inventory of Depression Symptomatology-16 items Self-Report (QIDS-16-SR) total scores, and other outcome measures were analyzed with the last observation carried forward strategy and/or mixed-effects modeling for repeated measures. Results Of the 34 patients screened, 23 patients were randomized to receive quetiapine-XR (n = 11) or placebo (n = 12), with 5 and 4 completing the study, respectively. The mean dose of quetiapine-XR was 154 ± 91 mg/d. The change from baseline to endpoint in the total scores of HAMD-17, HAM-A, QIDS-16-SR, and CGI-S were significant in the quetiapine-XR group, but only the change in HAM-A total score was significant in the placebo group. The differences in these changes between the two groups were only significant in CGI-S scores, with the rest of numerical larger in the quetiapine-XR group. The most common side effects from quetiapine-XR were dry mouth, somnolence/sedation, and fatigue. Conclusions In this pilot study, quetiapine-XR was numerically superior to placebo in reducing depressive and anxiety symptoms in patients with MDD and current GAD. Large sample studies are warranted to support or refute these preliminary findings. PMID:27738370

  10. Consensus Interferon for Recurrent Hepatitis C Infection in Nonresponders to Peginterferon and Ribavirin After Liver Transplant.

    PubMed

    Nordstrom, Eric M; Biggins, Scott W; Gralla, Jane; Rosen, Hugo R; Everson, Gregory T; Burton, James R

    2015-12-01

    Hepatitis C virus infection universally recurs in liver transplant recipients. Peginterferon/ribavirin achieves a sustained virologic response rate of 30% in recipients infected with hepatitis C virus genotype 1. Consensus-interferon plus ribavirin yields sustained virologic response rates to 30% in patients failing to achieve sustained virologic response with peginterferon/ribavirin pretransplant, but it has not been studied posttransplant. We sought to evaluate the efficacy and tolerability of consensus-interferon and ribavirin in treating posttransplant hepatitis C virus. Clinical, laboratory, and virologic data were collected retrospectively from all patients who received at least 1 dose of consensus-interferon after transplant between January 2008 and December 2011. A standardized treatment protocol was used. The primary aim was sustained virologic response defined by undetectable hepatitis C virus RNA at 24 weeks after completing therapy. Twenty-three patients were treated with consensus-interferon/ribavirin; 15 with prior nonresponse (87%) or breakthrough (6.7%) during peginterferon/ribavirin, and 8 as initial therapy. The intention-to-treat sustained virologic response with consensus-interferon was 30%. Anemia, leukopenia, and growth factor requirement were similar between peginterferon and consensus-interferon cohorts. Consensus-interferon may rescue liver recipients who are nonresponders to peginterferon-based therapy. The efficacy of interferon-based treatment regimens may benefit from substitution of consensus-interferon for peginterferon.

  11. Major depressive disorder, antidepressants, and sexual dysfunction.

    PubMed

    Clayton, Anita H; Montejo, Angel L

    2006-01-01

    Sexual dysfunction is a common problem with a number of causes, including psychosocial factors, general medical illness, psychiatric disorders, and psychotropic and nonpsychiatric medications. It is especially prevalent among patients with poor emotional health and has been strongly associated with antidepressant medications. Selective serotonin reuptake inhibitors (SSRIs) in particular have demonstrated a higher incidence of sexual dysfunction than other antidepressants that work through different mechanisms of action. Further supporting the relationship between sexual dysfunction and antidepressant mechanism of action, data from a number of studies indicate that bupropion, nefazodone, and mirtazapine alleviate symptoms of sexual dysfunction and are as effective as SSRIs at controlling depressive symptoms. Although a number of strategies besides drug substitution have been utilized to help manage antidepressant-induced sexual dysfunction, many patients remain suboptimally treated; as many as 42% of patients were found to passively wait for spontaneous remission. The addition of antidotal therapy has been proven to be among the effective management strategies for sexual dysfunction. However, due to a lack of systematic data, additional studies are warranted to further investigate these findings.

  12. Antidepressant Augmentation Using the NMDA-Antagonist Memantine: A Randomized, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    Smith, Eric G.; Deligiannidis, Kristina M.; Ulbricht, Christine M.; Landolin, Chelsea S.; Patel, Jayendra K.; Rothschild, Anthony J.

    2014-01-01

    Objective Intravenous NMDA antagonists have shown promising results in rapidly ameliorating depression symptoms, but placebo-controlled trials of oral NMDA antagonists as monotherapy have not observed efficacy. We conducted a randomized, double-blind, placebo-controlled trial (NCT00344682) of the NMDA antagonist memantine as an augmentation treatment for patients with DSM-IV major depressive disorder. Method 31 participants with partial or nonresponse to their current antidepressant were randomized (from 2006–2011) to add memantine (flexible dose 5–20 mg/day, with all memantine group participants reaching the dose of 20 mg/day) (n= 15) or placebo (n= 16) to their existing treatment for 8 weeks. The primary outcome, change in Montgomery-Asberg Depression Rating Score (MADRS), was evaluated with repeated measures mixed effects models using last-observation-carried-forward methods. Secondary outcomes included other depression and anxiety rating scales, suicidal and delusional ideation, and other adverse effects. Results Participants receiving memantine did not show a statistically or clinically significant change in MADRS scores compared to placebo, either over the entire study (β=0.133, favoring placebo, p=0.74) or at study completion (week 8 MADRS score change: −7.13 +/−6.61 (memantine); −7.25 +/−11.14 (placebo), p=0.97). A minimal-to-small effect size (comparing change to baseline variability) was observed (d=0.19), favoring placebo. Similarly, no substantial effect sizes favoring memantine, nor statistically significant between-group differences, were observed on secondary efficacy or safety outcomes. Conclusions This trial did not detect significant statistical or effect size differences between memantine and placebo augmentation among nonresponders or poor responders to conventional antidepressants. While the small number of participants is a limitation, this study suggests memantine lacks substantial efficacy as an augmentation treatment against

  13. Non-responders to egg grown influenza vaccine seroconvert after booster immunization with MDCK cell grown vaccine.

    PubMed

    Oxford, John S; Al-Jabri, Ali A; Lambkin, Robert; Palache, A M; Fleming, D M

    2003-06-20

    We have investigated whether 'at risk' subjects who did not respond serologically during a pre-study vaccination with a commercial egg grown influenza sub-unit vaccine would respond to a subsequent vaccination with either a single dose of MDCK cell grown influenza vaccine or a standard egg grown influenza vaccine containing the same virus strains. We studied 48 non-responder subjects with a mean age 67.5, range: 34-82 years. In this non-responder group the increased immune response that was detected after boosting with an MDCK cell derived vaccine response was variable and relatively modest, except for the A/Texas strain in the vaccine. The proportion of subjects, with an HI titre of >/=40 (protective antibody titre) increased from 50 to 83% (A/Texas strain), from 13 to 25% (B/Harbin strain) and from 38 to 46% (A/Wuhan strain). In comparison a booster vaccination with egg-derived influenza vaccine resulted in an increase immune response with an HI antibody titre >/=40 for two of the three strains, namely from 17 to 58% for the B/Harbin strain and from 8 to 33% for the A/Wuhan strain.

  14. Use of venlafaxine compared with other antidepressants and the risk of sudden cardiac death or near death: a nested case-control study.

    PubMed

    Martinez, Carlos; Assimes, Themistocles L; Mines, Daniel; Dell'aniello, Sophie; Suissa, Samy

    2010-02-05

    To assess whether use of the antidepressant venlafaxine is associated with an increased risk of sudden cardiac death or near death compared with other commonly used antidepressants. Population based observational study. We did a nested case-control analysis within a new user cohort formed using the United Kingdom General Practice Research Database. New users of venlafaxine, fluoxetine, citalopram, or dosulepin on or after 1 January 1995, aged 18 to 89 years, with a diagnosis of depression or anxiety. Participants were followed-up until February 2005, or the occurrence of sudden cardiac death or near death, identified from medical records indicating non-fatal acute ventricular tachyarrhythmia, sudden death due to cardiac causes, or out of hospital deaths from acute ischaemic cardiac events. For each case, 30 controls were selected matched for age, sex, calendar time, and indication. We used conditional logistic regression to calculate the adjusted odds ratio of sudden cardiac death or near death associated with current use of venlafaxine compared with current use of fluoxetine, citalopram or dosulepin. 207 384 participants were followed-up for an average of 3.3 years. There were 568 cases of sudden cardiac death or near death, which were matched to 14 812 controls. The adjusted odds ratio of sudden cardiac death or near death associated with venlafaxine use was 0.66 (95% confidence interval 0.38 to 1.14) relative to fluoxetine use, whereas compared with citalopram it was 0.89 (0.50 to 1.60) and with dosulepin 0.83 (0.46 to 1.52). In this large, population based study, the use of venlafaxine was not associated with an excess risk of sudden cardiac death or near death compared with fluoxetine, dosulepin, or citalopram, in patients with depression or anxiety.

  15. Adjunctive Lanicemine (AZD6765) in Patients with Major Depressive Disorder and History of Inadequate Response to Antidepressants: A Randomized, Placebo-Controlled Study.

    PubMed

    Sanacora, Gerard; Johnson, Michael R; Khan, Arif; Atkinson, Sarah D; Riesenberg, Robert R; Schronen, Juan P; Burke, Michael A; Zajecka, John M; Barra, Luis; Su, Hong-Lin; Posener, Joel A; Bui, Khanh H; Quirk, Michael C; Piser, Timothy M; Mathew, Sanjay J; Pathak, Sanjeev

    2017-03-01

    The objective of this study was to investigate the efficacy and safety of adjunctive lanicemine (NMDA channel blocker) in the treatment of major depressive disorder (MDD) over 12 weeks. This phase IIb, randomized, parallel-arm, double-blind, placebo-controlled study was conducted at 49 centers in four countries between December 2011 and August 2013 in 302 patients aged 18-70 years, meeting criteria for single episode or recurrent MDD and with a history of inadequate treatment response. Patients were required to be taking an allowed antidepressant for at least four weeks prior to screening. Patients were randomized equally to receive 15 double-blind intravenous infusions of adjunctive lanicemine 50 mg, lanicemine 100 mg, or saline over a 12-week course, in addition to ongoing antidepressant. The primary efficacy end point was change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to week 6. Secondary efficacy outcome variables included change in MADRS score from baseline to week 12, response and remission rates, and changes in Clinical Global Impression scale, Quick Inventory of Depressive Symptomology Self-Report score, and Sheehan Disability Scale score. Of 302 randomized patients, 240 (79.5%) completed treatment. Although lanicemine was generally well tolerated, neither dose was superior to placebo in reducing depressive symptoms on the primary end point or any secondary measures. There was no significant difference between lanicemine and placebo treatment on any outcome measures related to MDD. Post hoc analyses were performed to explore the possible effects of trial design and patient characteristics in accounting for the contrasting results with a previously reported trial.

  16. Adjunctive Lanicemine (AZD6765) in Patients with Major Depressive Disorder and History of Inadequate Response to Antidepressants: A Randomized, Placebo-Controlled Study

    PubMed Central

    Sanacora, Gerard; Johnson, Michael R; Khan, Arif; Atkinson, Sarah D; Riesenberg, Robert R; Schronen, Juan P; Burke, Michael A; Zajecka, John M; Barra, Luis; Su, Hong-Lin; Posener, Joel A; Bui, Khanh H; Quirk, Michael C; Piser, Timothy M; Mathew, Sanjay J; Pathak, Sanjeev

    2017-01-01

    The objective of this study was to investigate the efficacy and safety of adjunctive lanicemine (NMDA channel blocker) in the treatment of major depressive disorder (MDD) over 12 weeks. This phase IIb, randomized, parallel-arm, double-blind, placebo-controlled study was conducted at 49 centers in four countries between December 2011 and August 2013 in 302 patients aged 18–70 years, meeting criteria for single episode or recurrent MDD and with a history of inadequate treatment response. Patients were required to be taking an allowed antidepressant for at least four weeks prior to screening. Patients were randomized equally to receive 15 double-blind intravenous infusions of adjunctive lanicemine 50 mg, lanicemine 100 mg, or saline over a 12-week course, in addition to ongoing antidepressant. The primary efficacy end point was change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to week 6. Secondary efficacy outcome variables included change in MADRS score from baseline to week 12, response and remission rates, and changes in Clinical Global Impression scale, Quick Inventory of Depressive Symptomology Self-Report score, and Sheehan Disability Scale score. Of 302 randomized patients, 240 (79.5%) completed treatment. Although lanicemine was generally well tolerated, neither dose was superior to placebo in reducing depressive symptoms on the primary end point or any secondary measures. There was no significant difference between lanicemine and placebo treatment on any outcome measures related to MDD. Post hoc analyses were performed to explore the possible effects of trial design and patient characteristics in accounting for the contrasting results with a previously reported trial. PMID:27681442

  17. LC-MS/MS based studies on the anti-depressant effect of hypericin in the chronic unpredictable mild stress rat model.

    PubMed

    Zhai, Xue-jia; Chen, Fen; Chen, Chen; Zhu, Chao-ran; Lu, Yong-ning

    2015-07-01

    St John׳s Wort (Hypericum perforatum, SJW) is a widely used herbal medicine in western countries but also an important Uygur drug in China. Hypericin (HY) is the main components in SJW extracts, which is used to treat fatigue, weakness, and mild depression. The aim of this study was to investigate the anti-depression effects of HY on chronic unpredictable mild stress (CUMS) model rats and identify the possible mechanisms. In this study, the protective effects of HY on CUMS-induced depression in rats were investigated by using a combination of behavioral assessments and urinary metabolites analysis. Urinary metabolites analyses were performed using LC-MS/MS in conjunction with principal components analysis (PCA) after oral administration of either HY or Venlafaxine (VF) for 27 days. During the procedure of experiment, food consumption, body weight, adrenal gland, thymus and spleen indices, behavior scores, sucrose consumption, and stress hormone levels were measured. Changes in the classic behavioral tests and pharmacological biochemical indices reflected that HY alleviated the symptoms of depression in a shorter period than VF, which was used as positive control for antidepression. Metabolites analysis of urine revealed that HY affected excitatory amino acids and monoamine neurotransmitter metabolites. Remarkably, urinary valine was increased remarkably by HY, even much higher than CUMS group. These results provide important mechanistic insights into the protective effects of HY against CUMS-induced depression and metabolic dysfunction. As the most important active ingredient in SJW extracts, HY possesses the better protective effect against CUMS-induced depression symptoms and metabolic disturbances. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. A Qualitative Analysis of the Perception of Stigma Among Latinos Receiving Antidepressants

    PubMed Central

    Interian, Alejandro; Martinez, Igda E.; Guarnaccia, Peter J.; Vega, William A.; Escobar, Javier I.

    2008-01-01

    Objective This study sought to describe the role of stigma in antidepressant adherence among Latinos. Methods The study utilized data generated from six focus groups of Latino outpatients receiving antidepressants (N=30). By using a grounded theory approach, qualitative analysis focused specifically on the role of stigma in antidepressant treatment, as well as salient Latino values. Results Perceptions of stigma were related to both the diagnosis of depression and use of antidepressant medication. Qualitative analyses showed that antidepressant use was seen as implying more severe illness, weakness or failure to cope with problems, and being under the effects of a drug. Reports of stigma were also related to social consequences. Also, the perceived negative attributes of antidepressant use were at odds with self-perceived cultural values. Conclusions Stigma was a prominent concern among Latinos receiving antidepressants, and stigma often affected adherence. Furthermore, culture is likely to play an important role in the communication of stigma and its associated complications. PMID:18048562

  19. Antidepressants in the general hospital.

    PubMed Central

    Gelenberg, A. J.

    1979-01-01

    An approach to the use of antidepressant medication in the general hospital is presented. The type of depression most likely to respond to chemotherapy is described, categories of available antidepressant agents are discussed, and relevant pharmacologic aspects are outlined. This paper suggests clinical guidelines for the use of these drugs, particularly in medical and surgical patients. PMID:455184

  20. Evaluating the tolerability of the newer antidepressants.

    PubMed

    Dewan, M J; Anand, V S

    1999-02-01

    Given their equal efficacy, the choice of a specific antidepressant is largely influenced by side effect (SE) profiles. A number of new agents have recently become available. However, data directly comparing the side effects of these agents are scarce. As suggested by AHCPR guidelines, we used the 1998 Physicians' Desk Reference (PDR) to construct a comparison table using treatment emergent, placebo-adjusted incidence rates for the major (gastrointestinal, central nervous system, and sexual) side effects caused by nine antidepressants (fluoxetine, paroxetine, sertraline, fluvoxamine, nefazodone, bupropion SR, mirtazapine, venlafaxine XR, and citalopram). The results were tabulated to show the relative propensity of each drug to cause a particular side effect. Bupropion SR had the most favorable overall side-effect profile, and fluvoxamine the least favorable. However, there are several limitations in using the PDR to compare the newer antidepressants. Clinical studies directly comparing SEs of newer antidepressants are needed. Sexual SEs substantially affected total SE liability. A simplified summary table, with its advantages and some limitations, is not simple to construct. Pitfalls in this process are discussed.

  1. Characteristics of clinical measurements between biomechanical responders and non-responders to a shoe designed for knee osteoarthritis.

    PubMed

    Kim, Yongwook; Richards, Jim; Lidtke, Roy H; Trede, Renato

    2017-09-29

    The purpose of this study was to investigate the characteristics of biomechanical and clinical measurements in relation to the knee adduction moment when wearing a standard shoe and a shoe design for individuals with knee osteoarthritis (Flex-OA). Kinematic and kinetic data were collected from thirty-two healthy individuals (64 knees) using a ten camera motion analysis system and four force plates. Subjects performed 5 walking trials under the two conditions and the magnitude of individuals' biomechanical responses where explored in relation to the clinical assessment of the Foot Posture Index, hip rotation range, strength of hip rotators, and active ankle-foot motion, all of which have been described as possible compensation mechanisms in knee osteoarthritis. Significant reductions in the first peak of the knee adduction moment (KAM) during stance phase (9.3%) were recorded (p<0.0001). However, despite this difference, 22 of 64 knees showed either no change or an increased KAM, indicating a non-response or negative-response to the Flex-OA shoe. Significant differences were observed between the responder and non-responder subgroups in the hip rotation range ratio (p=0.044) and the hip rotators strength ratio (p=0.028). Significant differences were seen in clinical assessments of hip rotation range and hip rotator strength between responders and non-responders using a cut-off of 0.02Nm/kg change in the KAM. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Parents' difficulties as co-therapists in CBT among non-responding youths with anxiety disorders: Parent and therapist experiences.

    PubMed

    Lundkvist-Houndoumadi, Irene; Thastum, Mikael; Nielsen, Klaus

    2016-07-01

    No increased effect has been associated with parent involvement in cognitive behavioral therapy (CBT) for youths with anxiety disorders. The purpose of this study was to explore parent and therapist experiences of CBT among non-responding youths with anxiety disorders, with a primary focus on parent involvement in therapy. Interpretative phenomenological analysis was applied to 24 sets of semi-structured interviews with families and therapists of anxiety-disordered youths who had not profited from CBT with parental inclusion. From the superordinate theme parents' difficulties acting as co-therapists, which emerged from the analyses, two master themes represented the perspectives of parents (difficulty working together with the youth and feeling unqualified, with limited resources), and two represented the perspectives of therapists (family dynamics stood in the way of progress and difficulty transferring control to parents). Parent and therapist experiences complemented each other, offering two different perspectives on parent difficulties as co-therapists. However, the two groups' views on their respective roles in therapy were in conflict. Parents wished to remain being "just the parents" and for the experts to take over, while therapists wished to act as facilitators transferring the control to parents. Clinical implications are drawn for parental involvement and enhancement of treatment outcomes for likely non-responders. © The Author(s) 2015.

  3. Phytochemical constituents as future antidepressants: a comprehensive review.

    PubMed

    Bahramsoltani, Roodabeh; Farzaei, Mohammad Hosein; Farahani, Marzieh Sarbandi; Rahimi, Roja

    2015-01-01

    Depression is a major mental disease that is ranked as the fourth leading cause of disability. In order to avoid unwanted adverse reactions, as well as improve efficacy, current researches are seeking alternatives to conventional antidepressants. Phytochemicals provide an extensive research area in antidepressant therapies. The aim of the present study is to comprehensively review neurological evidences demonstrating the efficacy of phytochemicals in depression. For this purpose, electronic databases were searched to collect all data on the antidepressant mechanisms of phytochemicals from 1966 up to 2015. Plant metabolites from different categories including polyphenols (flavonoids, phenolic acids, lignanes, coumarins), alkaloids, terpenes and terpenoids, saponins and sapogenins, amines, and carbohydrates were found to possess antidepressant activity. Naringenin, quercetin derivatives, eugenol, piperine, diterpene alkaloids, berberine, hyperforin, riparin derivatives, ginsenosides, as well as β-carboline alkaloids are among the most relevant ones. Naringenin has represented its antidepressant effect by elevation of serotonin (5-HT), norepinephrine, brain-derived neurotrophic factor (BDNF), and glucocorticoid receptors. Piperine demonstrated inhibition of monoamine oxidase enzymes, elevation of brain 5-HT and BDNF levels, and modulation of the hypothalamus-pituitary-adrenal axis. The serotonergic, noradrenergic, and dopaminergic effect of berberine has been proven in several studies. Quercetin derivatives have revealed antidepressant potential via elevating pro-opiomelanocortin and neuroprotective properties, as well as reduction of proinflammatory cytokines. Assessing the structure-activity relationship of highly potent antidepressant phytochemicals is suggested to find future natural, semisynthetic, or synthetic antidepressants. Further clinical studies are also necessary for confirmation of natural antidepressant efficacy and completion of their safety profile.

  4. Mirtazapine, an antidepressant.

    PubMed

    Puzantian, T

    1998-01-01

    The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of mirtazapine are reviewed. Mirtazapine is a new anti-depressant that blocks presynaptic alpha 2-adrenergic receptors and postsynaptic serotonin type 2 and type 3 receptors. Mirtazapine has FDA-approved labeling for treatment of depression. Limited data suggest it may also have beneficial anxiolytic and sedative effects. The drug is rapidly and completely absorbed after oral administration. It is biotransformed by hepatic demethylation and is suitable for once-daily doses. In several clinical trials, patients receiving mirtazapine showed significantly greater improvement as measured by scores on the Hamilton Rating Scale for Depression (HAM-D) compared with patients receiving placebo. Mirtazapine has been shown to be equally efficacious as amitriptyline, clomipramine, and doxepin as assessed by scores on the HAM-D or other depression rating scales. Mirtazapine is well tolerated. The most commonly reported adverse effects associated with mirtazapine are somnolence, increased appetite, weight gain, and dizziness. Few drug-drug interactions have been reported. The recommended starting dosage is 15 mg/day administered in a single dose at bedtime. Mirtazapine seems to be an effective, well-tolerated antidepressant and may be effective for treating comorbid anxiety disorders.

  5. Antidepressant effect of Stillen.

    PubMed

    Jeong, Hyun-Ja; Kim, Jeong-Hwa; Kim, Na-Rae; Yoou, Myoung-schook; Nam, Sun-Young; Kim, Kyu-Youb; Choi, Youngjin; Jang, Jae-Bum; Kang, In-Cheol; Baek, Nam-In; Kim, Hyung-Min

    2015-06-01

    Stillen has been used to treat patients with gastric mucosal ulcers and has an anti-inflammatory effect. It is well-known that neuro-inflammatory reactions are related to depression. Here we evaluated the antidepressant-like effect of Stillen on mice subjected to the forced swimming test (FST). Stillen and eupatilin (a major component of Stillen) significantly decreased immobility times compared with the FST control group. In the Stillen-administered group, increased levels of 5-hydroxytryptamine (serotonin) and brain-derived neurotrophic factor protein were observed in the hippocampus. Nissl bodies also increased in the hippocampus neuronal cytoplasm of the Stillen-administered group. Stillen decreased levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (at the mRNA and protein levels) in the hippocampus and serum, compared with the control group. In addition, the mRNA expression of estrogen receptor-β increased after Stillen administration in the hippocampus. These findings suggest that Stillen should be viewed as a candidate antidepressant.

  6. Consensus interferon and ribavirin in patients with chronic hepatitis C who were nonresponders to pegylated interferon alfa-2b and ribavirin.

    PubMed

    Leevy, Carroll B

    2008-07-01

    Recent studies suggest that consensus interferon and ribavirin is effective in retreating patients with chronic hepatitis C who failed therapy with interferon alfa and ribavirin. The objective of the present study was to assess the efficacy, safety, and tolerability of consensus interferon and ribavirin in patients who did not respond to pegylated interferon alfa-2b and ribavirin. We retrospectively identified 137 consecutive nonresponders to pegylated interferon alfa-2b and ribavirin and initiated patients on daily treatment with consensus interferon 15 mug subcutaneously and weight-based ribavirin for 48 weeks. If patients were HCV RNA negative at 12 weeks, the dose was reduced to 15 mug three times weekly for the remaining 36 weeks. The sustained virologic response rate was 37%. Daily consensus interferon therapy was safe and well tolerated in all patients. No dose reductions were required, and no patient discontinued therapy. Further studies of consensus interferon and ribavirin in nonresponders are warranted.

  7. Gender display in Scandinavian and American advertising for antidepressants.

    PubMed

    Lövdahl, U; Riska, A; Riska, E

    1999-12-01

    This study examines whether depiction of users of antidepressants in advertisements for antidepressants in the 1995 issues of the major medical journal in each of Denmark, Finland, Norway, and Sweden differs from that in the American Journal of Psychiatry. The results show that the people shown in the Danish, Finnish, and Norwegian journals are predominantly women, whereas depiction of users in the American and Swedish advertising is predominantly of couples. The portrayals in the 1995 advertising are of antidepressants as female gendered; a feature that was not seen in advertising for psychotropic drugs in the Nordic countries in the 1980s.

  8. Do depressed patients on adjunctive atypical antipsychotics demonstrate a better quality of life compared to those on antidepressants only? A comparative cross-sectional study of a nationally representative sample of the US population.

    PubMed

    Al-Ruthia, Yazed Sulaiman; Hong, Song Hee; Solomon, David

    2015-01-01

    The adjunctive use of some atypical antipsychotics (AAPs) has been popular for patients with treatment-resistant depression. However, little is known about the impact of these agents on patients' Health-related quality of life (HRQoL). The objective of this study is to examine the impact of the adjunctive AAPs use on HRQoL among users of antidepressants with self-reported depression. Patients with depression (ICD-9-CM: 296, 300, and 311), and to have used the given AAPs and/or antidepressants for at least a year, were identified in the Medical Expenditure Panel Survey of 2008-2011. The patients were classified into users of adjunctive AAPs (i.e., antidepressants plus AAPs) and users of antidepressants only. Adjusted multivariate linear regression analyses were conducted to examine the association between the utilization of AAPs and HRQoL measure.(c) A total of 3638 participants who met the inclusion criteria were identified (306 on AAPs vs. 3332 on antidepressants only). The study subjects were ≥18 years, predominately White (91.9%) and female (71%). The AAPs utilization was not associated with higher scores in the Physical Component Summary (PCS-12) of the Short Form Health Survey (SF-12v2) (β = 1.542, 95% CI = -0.0142 to 3.0977, P = 0.0521). Rather, it was negatively associated with the Mental Component Summary (MCS-12) scores of the SF-12v2 (β = -1.5537, 95% CI = -3.0247 to -0.0827, P = 0.0385). The utilization of AAPs was not associated with higher scores of HRQoL. The findings of this study should underscore the need to consider other treatment options as add-on therapy for depression before resorting to AAPs. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Understanding Faculty Survey Nonrespondents: Their Characteristics, Organizational Citizenship Behaviors, Workplace Attitudes, and Reasons for Nonparticipation

    ERIC Educational Resources Information Center

    Mathews, Kiernan Robert

    2013-01-01

    College and university administrators frequently survey their faculty to inform decisions affecting the academic workplace. Higher education researchers, too, rely heavily on survey methodologies in their scholarly work. Survey response rates, however, have been declining steadily for decades, and when nonrespondents and respondents systematically…

  10. Understanding Faculty Survey Nonrespondents: Their Characteristics, Organizational Citizenship Behaviors, Workplace Attitudes, and Reasons for Nonparticipation

    ERIC Educational Resources Information Center

    Mathews, Kiernan Robert

    2013-01-01

    College and university administrators frequently survey their faculty to inform decisions affecting the academic workplace. Higher education researchers, too, rely heavily on survey methodologies in their scholarly work. Survey response rates, however, have been declining steadily for decades, and when nonrespondents and respondents systematically…

  11. Antecedent life events, social supports and response to antidepressants in depressed patients.

    PubMed

    Tomaszewska, W; Peselow, E D; Barouche, F; Fieve, R R

    1996-11-01

    We evaluated 355 subjects who entered one of six double-blind placebo-controlled antidepressant drug trials with respect to the occurrence of antecedent adverse life events and their meaning to the patient. Patients were also assessed with regard to the degree of social support they received for the negative life event. The groups differed as to whether they did or did not meet the criteria for melancholic depression; 43 one-week placebo responders were statistically significantly more likely to believe that adverse life events predisposed them to depressive illness and that such life events precipitated their current depression, compared to 312 one-week placebo non-responders. Of the 312 patients who went on to the double-blind phase in which they were treated with either drug (n = 204) or placebo (n = 108), it was noted that, for both melancholic and non-melancholic patients, responders to drug treatment (but not placebo) had a more favourable ratio of social support received/social support desired than non-responders. Non-melancholic responders to both drug and placebo were statistically significantly more likely to report fewer adverse life events and have a less strong belief that adverse life events predispose one to depressive illness than non-responders. Melancholic patients did not show this trend.

  12. [Antidepressants in the elderly].

    PubMed

    Cortajarena García, M C; Ron Martin, S; Miranda Vicario, E; Ruiz de Vergara Eguino, A; Azpiazu Gomez, P J; Lopez Aldana, J

    2016-10-01

    Depression in the elderly is a changing, difficult and common disorder. At this age, there are more relapses and more long-life treatment is required. The pharmacology approach is a challenge because of concurrent factors that make their treatment more difficult. It is very important to have a basic antidepressant scheme, in order to help treat this disorder with efficiency and success from Primary Care. There are no drugs without side effects, and their characteristics have to be known in order to make the right selection depending on effectiveness, safety and tolerance. Copyright © 2015 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  13. More female patients and fewer stimuli per session are associated with the short-term antidepressant properties of repetitive transcranial magnetic stimulation (rTMS): a meta-analysis of 54 sham-controlled studies published between 1997–2013

    PubMed Central

    Kedzior, Karina Karolina; Azorina, Valeriya; Reitz, Sarah Kim

    2014-01-01

    Background Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) appears to have short-term antidepressant properties. The aim of the current study was to update our previous meta-analysis and to investigate factors associated with the antidepressant properties of rTMS. Method Following a systematic literature search conducted in Medline and PsycInfo, N=14 sham-controlled, parallel design studies (published after 2008 to August 2013) that had utilized rTMS of the DLPFC in major depression were included in the current meta-analysis. The sensitivity and moderator analyses also included data from N=40 studies (published in 1997–2008) from our previous meta-analysis. The effect size (Cohen’s d) in each study was the standardized difference in mean depression scores (on Hamilton Depression Rating Scale, Beck Depression Inventory, Montgomery Åsberg Depression Rating Scale) from baseline to final (after last session) in rTMS compared to sham groups. Results According to a random-effects model with inverse-variance weights, depression scores were significantly reduced after rTMS compared to sham in studies published from 2008–2013 based on N=659 patients (overall mean weighted d=−0.42, 95% confidence interval: −0.66, −0.18, P=0.001). Combining studies from our past and current meta-analyses (published in 1997–2013; N=54) revealed that depression was significantly reduced after left-fast (>1 Hz), right-slow (≤1 Hz), and bilateral (or sequential) rTMS of DLPFC compared to sham. Significant antidepressant properties of rTMS were observed in studies with patients who were treatment resistant, unipolar (or bipolar), non-psychotic, medication-free (or started on antidepressants concurrently with rTMS). According to univariate meta-regressions, depression scores were significantly lower in studies with more female patients and fewer stimuli per session. There was little evidence that publication bias occurred in the

  14. Changes in lumbar multifidus muscle function and nociceptive sensitivity in low back pain patient responders versus non-responders after dry needling treatment.

    PubMed

    Koppenhaver, Shane L; Walker, Michael J; Su, Jonathan; McGowen, Jared M; Umlauf, Lindsey; Harris, Kevin D; Ross, Michael D

    2015-12-01

    Little is known about the physiologic mechanism of dry needling. While some evidence suggests that dry needling may decrease nocioceptive sensitivity and facilitate muscle function, no studies to date have examined these physiologic changes compared to clinical outcomes. To examine changes in lumbar multifidus (LM) muscle function and nociceptive sensitivity after dry needling in patients with LBP and to determine if such changes differ in patients that exhibit improved disability (responders) and those that do not (non-responders). Quasi-experimental study. Sixty-six volunteers with mechanical LBP (38 men, age = 41.3 ± 9.2 years) completed the study. Ultrasound measurements and pain algometry of the LM were taken at baseline and repeated immediately following dry needling treatment to the LM muscles and after one week. The percent change in muscle thickness from rest to contraction was calculated for each time point to represent muscle function. Pressure pain threshold (PPT) was used to measure nociceptive sensitivity. Participants were dichotomized as responders and non-responders based on whether or not they experienced clinical improvement using the modified Oswestry Disability Index after one week. 2 × 3 mixed-model ANOVA were conducted for group (responders vs. non-responders) by time. Patient responders exhibited larger improvements in LM muscle contraction and nociceptive sensitivity 1 week, but not immediately, after dry needling than non-responders. Our results suggest that there may be lasting and clinically relevant sensorimotor changes that occur in LBP patients that improve with dry needling treatment that partially explain the physiologic mechanism of action. Published by Elsevier Ltd.

  15. Differing antidepressant maintenance methodologies.

    PubMed

    Safer, Daniel J

    2017-10-01

    The principle evidence that antidepressant medication (ADM) is an effective maintenance treatment for adults with major depressive disorder (MDD) is from placebo substitution trials. These trials enter responders from ADM efficacy trials into randomized, double-blind placebo-controlled (RDBPC) effectiveness trials to measure the rate of MDD relapse over time. However, other randomized maintenance trial methodologies merit consideration and comparison. A systematic review of ADM randomized maintenance trials included research reports from multiple databases. Relapse rate was the main effectiveness outcome assessed. Five ADM randomized maintenance methodologies for MDD responders are described and compared for outcome. These effectiveness trials include: placebo-substitution, ADM/placebo extension, ADM extension, ADM vs. psychotherapy, and treatment as usual. The placebo-substitution trials for those abruptly switched to placebo resulted in unusually high (46%) rates of relapse over 6-12months, twice the continuing ADM rate. These trials were characterized by selective screening, high attrition, an anxious anticipation of a switch to placebo, and a risk of drug withdrawal symptoms. Selectively screened ADM efficacy responders who entered into 4-12month extension trials experienced relapse rates averaging ~10% with a low attrition rate. Non-industry sponsored randomized trials of adults with multiple prior MDD episodes who were treated with ADM maintenance for 1-2years experienced relapse rates averaging 40%. Placebo substitution trial methodology represents only one approach to assess ADM